Difference between revisions of "Role of ubiquitination"

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(Autoloading by CXLParser)
(Autoloading by CXLParser)
 
(4 intermediate revisions by the same user not shown)
Line 6: Line 6:
 
URL="#1J1D8B0LY-77N6FX-5FN",
 
URL="#1J1D8B0LY-77N6FX-5FN",
 
label="Methylglyoxal",
 
label="Methylglyoxal",
pos="21.54,-10.68!",
+
pos="2.99,-10.33!",
 
width=1.44,
 
width=1.44,
 
height=0.67,
 
height=0.67,
 
fontsize=12,
 
fontsize=12,
shape=circle, color="#ff0000ff"];
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shape=circle, fontcolor="#0000ffff", color="#000000ff"];
 
"1HXDY3N30-SXZ26V-89M" [id="1HXDY3N30-SXZ26V-89M",
 
"1HXDY3N30-SXZ26V-89M" [id="1HXDY3N30-SXZ26V-89M",
 
URL="#1HXDY3N30-SXZ26V-89M",
 
URL="#1HXDY3N30-SXZ26V-89M",
 
label="E2F",
 
label="E2F",
pos="11.5,-5.5!",
+
pos="12.03,-4.69!",
 
width=0.6,
 
width=0.6,
 
height=0.4,
 
height=0.4,
 
fontsize=12,
 
fontsize=12,
shape=oval, color="#808080ff"];
+
shape=circle, color="#ff00ffff"];
 
"1HXF3TMQM-73NBC5-FW0" [id="1HXF3TMQM-73NBC5-FW0",
 
"1HXF3TMQM-73NBC5-FW0" [id="1HXF3TMQM-73NBC5-FW0",
 
URL="#1HXF3TMQM-73NBC5-FW0",
 
URL="#1HXF3TMQM-73NBC5-FW0",
 
label="Ras",
 
label="Ras",
pos="9.46,-13.36!",
+
pos="5.71,-13.24!",
 
width=0.58,
 
width=0.58,
 
height=0.4,
 
height=0.4,
 
fontsize=12,
 
fontsize=12,
shape=oval, color="#ffff99ff"];
+
shape=circle, color="#ffff00ff"];
 
"1N9P66C3N-1KWKJKJ-1ZB3" [id="1N9P66C3N-1KWKJKJ-1ZB3",
 
"1N9P66C3N-1KWKJKJ-1ZB3" [id="1N9P66C3N-1KWKJKJ-1ZB3",
 
URL="#1N9P66C3N-1KWKJKJ-1ZB3",
 
URL="#1N9P66C3N-1KWKJKJ-1ZB3",
 
label="ATR",
 
label="ATR",
pos="8.01,-1.64!",
+
pos="8.07,-1.76!",
 
width=0.61,
 
width=0.61,
 
height=0.4,
 
height=0.4,
 
fontsize=12,
 
fontsize=12,
shape=oval, color="#ff0000ff"];
+
shape=circle, color="#ff0000ff"];
 
"1HXF3W5MJ-D3H95R-FXG" [id="1HXF3W5MJ-D3H95R-FXG",
 
"1HXF3W5MJ-D3H95R-FXG" [id="1HXF3W5MJ-D3H95R-FXG",
 
URL="#1HXF3W5MJ-D3H95R-FXG",
 
URL="#1HXF3W5MJ-D3H95R-FXG",
 
label="Proliferation",
 
label="Proliferation",
pos="9.44,-15.47!",
+
pos="5.69,-15.35!",
 
width=1.17,
 
width=1.17,
 
height=0.28,
 
height=0.28,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1J1D8K6B5-17RSFTK-5JW" [id="1J1D8K6B5-17RSFTK-5JW",
 
"1J1D8K6B5-17RSFTK-5JW" [id="1J1D8K6B5-17RSFTK-5JW",
 
URL="#1J1D8K6B5-17RSFTK-5JW",
 
URL="#1J1D8K6B5-17RSFTK-5JW",
 
label="Poliubiquitination of\n Ubiquitin ligase CHIP by E3",
 
label="Poliubiquitination of\n Ubiquitin ligase CHIP by E3",
pos="21.56,-13.33!",
+
pos="3,-12.99!",
 
width=2.5,
 
width=2.5,
 
height=0.51,
 
height=0.51,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXDX8QW4-8CH6YX-7M9" [id="1HXDX8QW4-8CH6YX-7M9",
 
"1HXDX8QW4-8CH6YX-7M9" [id="1HXDX8QW4-8CH6YX-7M9",
 
URL="#1HXDX8QW4-8CH6YX-7M9",
 
URL="#1HXDX8QW4-8CH6YX-7M9",
 
label="Availability of damaged DNA\nFor repair complexes",
 
label="Availability of damaged DNA\nFor repair complexes",
pos="8.53,-7.79!",
+
pos="9.33,-7.79!",
 
width=2.54,
 
width=2.54,
 
height=0.51,
 
height=0.51,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXLM05XC-1FSPCXC-17T" [id="1HXLM05XC-1FSPCXC-17T",
 
"1HXLM05XC-1FSPCXC-17T" [id="1HXLM05XC-1FSPCXC-17T",
 
URL="#1HXLM05XC-1FSPCXC-17T",
 
URL="#1HXLM05XC-1FSPCXC-17T",
 
label="Transcription of adaptation \nto hypoxia genes",
 
label="Transcription of adaptation \nto hypoxia genes",
pos="20.85,-4.58!",
+
pos="19.49,-4.51!",
 
width=2.47,
 
width=2.47,
 
height=0.51,
 
height=0.51,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1J2TTSY2L-Z3PR1X-12T" [id="1J2TTSY2L-Z3PR1X-12T",
 
"1J2TTSY2L-Z3PR1X-12T" [id="1J2TTSY2L-Z3PR1X-12T",
 
URL="#1J2TTSY2L-Z3PR1X-12T",
 
URL="#1J2TTSY2L-Z3PR1X-12T",
 
label="FOXO1 deacetylation",
 
label="FOXO1 deacetylation",
pos="24.14,-6.18!",
+
pos="19.57,-6.89!",
 
width=1.9,
 
width=1.9,
 
height=0.32,
 
height=0.32,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXF3TF9N-2CNRBZM-FVR" [id="1HXF3TF9N-2CNRBZM-FVR",
 
"1HXF3TF9N-2CNRBZM-FVR" [id="1HXF3TF9N-2CNRBZM-FVR",
 
URL="#1HXF3TF9N-2CNRBZM-FVR",
 
URL="#1HXF3TF9N-2CNRBZM-FVR",
label="EGF-R",
+
label="EGFR",
pos="10.58,-12.26!",
+
pos="6.83,-12.14!",
width=0.79,
+
width=0.71,
 
height=0.39,
 
height=0.39,
 
fontsize=12,
 
fontsize=12,
Line 90: Line 90:
 
height=0.51,
 
height=0.51,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXDYCP8F-2BZCX14-8VY" [id="1HXDYCP8F-2BZCX14-8VY",
 
"1HXDYCP8F-2BZCX14-8VY" [id="1HXDYCP8F-2BZCX14-8VY",
 
URL="#1HXDYCP8F-2BZCX14-8VY",
 
URL="#1HXDYCP8F-2BZCX14-8VY",
 
label="E3 ubiquitin ligase complex \nRad6-Rad18",
 
label="E3 ubiquitin ligase complex \nRad6-Rad18",
pos="4.57,-2.01!",
+
pos="5.38,-2.01!",
 
width=2.74,
 
width=2.74,
 
height=1.14,
 
height=1.14,
 
fontsize=12,
 
fontsize=12,
shape=oval, color="#ffff99ff"];
+
shape=circle, color="#ffff00ff"];
 
"1HXDYPJ1C-RC1Z03-8X5" [id="1HXDYPJ1C-RC1Z03-8X5",
 
"1HXDYPJ1C-RC1Z03-8X5" [id="1HXDYPJ1C-RC1Z03-8X5",
 
URL="#1HXDYPJ1C-RC1Z03-8X5",
 
URL="#1HXDYPJ1C-RC1Z03-8X5",
 
label="PCNA",
 
label="PCNA",
pos="3.29,-4.82!",
+
pos="4.1,-4.82!",
 
width=0.72,
 
width=0.72,
 
height=0.39,
 
height=0.39,
 
fontsize=12,
 
fontsize=12,
shape=point, color="#000000ff"];
+
shape=hexagon, color="#00c8ffff"];
 
"1HXLLVYXK-YD59DQ-15R" [id="1HXLLVYXK-YD59DQ-15R",
 
"1HXLLVYXK-YD59DQ-15R" [id="1HXLLVYXK-YD59DQ-15R",
 
URL="#1HXLLVYXK-YD59DQ-15R",
 
URL="#1HXLLVYXK-YD59DQ-15R",
 
label="Ubiquitination and proteasome \nDegradation of HIF-1a",
 
label="Ubiquitination and proteasome \nDegradation of HIF-1a",
pos="20.85,-3.35!",
+
pos="19.49,-3.28!",
 
width=2.79,
 
width=2.79,
 
height=0.51,
 
height=0.51,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXDXCP6L-1JPNVC5-7R3" [id="1HXDXCP6L-1JPNVC5-7R3",
 
"1HXDXCP6L-1JPNVC5-7R3" [id="1HXDXCP6L-1JPNVC5-7R3",
 
URL="#1HXDXCP6L-1JPNVC5-7R3",
 
URL="#1HXDXCP6L-1JPNVC5-7R3",
 
label="DNA damage",
 
label="DNA damage",
pos="7.26,-0.35!",
+
pos="8.07,-0.35!",
 
width=1.25,
 
width=1.25,
 
height=0.32,
 
height=0.32,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXF3XKMD-1MDXYWM-FZ1" [id="1HXF3XKMD-1MDXYWM-FZ1",
 
"1HXF3XKMD-1MDXYWM-FZ1" [id="1HXF3XKMD-1MDXYWM-FZ1",
 
URL="#1HXF3XKMD-1MDXYWM-FZ1",
 
URL="#1HXF3XKMD-1MDXYWM-FZ1",
 
label="Monoubiquitination by ligase Cbl",
 
label="Monoubiquitination by ligase Cbl",
pos="11.64,-13.35!",
+
pos="7.89,-13.22!",
 
width=2.88,
 
width=2.88,
 
height=0.32,
 
height=0.32,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXDX70DD-C3RG63-7L2" [id="1HXDX70DD-C3RG63-7L2",
 
"1HXDX70DD-C3RG63-7L2" [id="1HXDX70DD-C3RG63-7L2",
 
URL="#1HXDX70DD-C3RG63-7L2",
 
URL="#1HXDX70DD-C3RG63-7L2",
 
label="ATP-dependent \nChromatin remodeling",
 
label="ATP-dependent \nChromatin remodeling",
pos="8.51,-6.28!",
+
pos="9.32,-6.28!",
 
width=2.03,
 
width=2.03,
 
height=0.51,
 
height=0.51,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1J2TTVWV5-1XB3QXN-15M" [id="1J2TTVWV5-1XB3QXN-15M",
 
"1J2TTVWV5-1XB3QXN-15M" [id="1J2TTVWV5-1XB3QXN-15M",
 
URL="#1J2TTVWV5-1XB3QXN-15M",
 
URL="#1J2TTVWV5-1XB3QXN-15M",
 
label="Ubiquitination and proteasome\n Degradation of FOXO1",
 
label="Ubiquitination and proteasome\n Degradation of FOXO1",
pos="24.15,-8.6!",
+
pos="19.58,-9.31!",
 
width=2.74,
 
width=2.74,
 
height=0.51,
 
height=0.51,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXDZ4FX8-1VG5BFM-92S" [id="1HXDZ4FX8-1VG5BFM-92S",
 
"1HXDZ4FX8-1VG5BFM-92S" [id="1HXDZ4FX8-1VG5BFM-92S",
 
URL="#1HXDZ4FX8-1VG5BFM-92S",
 
URL="#1HXDZ4FX8-1VG5BFM-92S",
 
label="DNA repair",
 
label="DNA repair",
pos="4.68,-7.71!",
+
pos="5.49,-7.71!",
 
width=2.64,
 
width=2.64,
 
height=0.72,
 
height=0.72,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXLLS50M-1PPGMX8-11F" [id="1HXLLS50M-1PPGMX8-11F",
 
"1HXLLS50M-1PPGMX8-11F" [id="1HXLLS50M-1PPGMX8-11F",
 
URL="#1HXLLS50M-1PPGMX8-11F",
 
URL="#1HXLLS50M-1PPGMX8-11F",
 
label="Normoxia",
 
label="Normoxia",
pos="20.85,-0.58!",
+
pos="19.49,-0.51!",
 
width=0.96,
 
width=0.96,
 
height=0.28,
 
height=0.28,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1N9P5YMFF-15HT175-1Z1Z" [id="1N9P5YMFF-15HT175-1Z1Z",
 
"1N9P5YMFF-15HT175-1Z1Z" [id="1N9P5YMFF-15HT175-1Z1Z",
 
URL="#1N9P5YMFF-15HT175-1Z1Z",
 
URL="#1N9P5YMFF-15HT175-1Z1Z",
label="PCNA",
+
label="PCNA\ngene",
pos="3.04,-6.38!",
+
pos="3.85,-6.38!",
 
width=0.61,
 
width=0.61,
height=0.28,
+
height=0.51,
 
fontsize=12,
 
fontsize=12,
 
shape=parallelogram, color="#008000ff"];
 
shape=parallelogram, color="#008000ff"];
Line 174: Line 174:
 
URL="#1HXF0TXZ0-2BJ3NZN-BJY",
 
URL="#1HXF0TXZ0-2BJ3NZN-BJY",
 
label="ARF",
 
label="ARF",
pos="1.26,-2.03!",
+
pos="2.07,-2.03!",
 
width=0.61,
 
width=0.61,
 
height=0.4,
 
height=0.4,
 
fontsize=12,
 
fontsize=12,
shape=oval, color="#ffff99ff"];
+
shape=circle, color="#ffff00ff"];
 
"1J1D8PQ19-MN9P7R-5P6" [id="1J1D8PQ19-MN9P7R-5P6",
 
"1J1D8PQ19-MN9P7R-5P6" [id="1J1D8PQ19-MN9P7R-5P6",
 
URL="#1J1D8PQ19-MN9P7R-5P6",
 
URL="#1J1D8PQ19-MN9P7R-5P6",
 
label="Disturbance of tissue resistance to hypoxia",
 
label="Disturbance of tissue resistance to hypoxia",
pos="21.61,-15.74!",
+
pos="3.06,-15.39!",
 
width=3.76,
 
width=3.76,
 
height=0.32,
 
height=0.32,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXDZVLBH-HRNZM1-9PT" [id="1HXDZVLBH-HRNZM1-9PT",
 
"1HXDZVLBH-HRNZM1-9PT" [id="1HXDZVLBH-HRNZM1-9PT",
 
URL="#1HXDZVLBH-HRNZM1-9PT",
 
URL="#1HXDZVLBH-HRNZM1-9PT",
 
label="Ubiquitination and proteasomal \nDegradation of hTERT",
 
label="Ubiquitination and proteasomal \nDegradation of hTERT",
pos="6.31,-12.63!",
+
pos="19.54,-11.85!",
 
width=2.83,
 
width=2.83,
 
height=0.51,
 
height=0.51,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXF261VH-3SS0BX-D11" [id="1HXF261VH-3SS0BX-D11",
 
"1HXF261VH-3SS0BX-D11" [id="1HXF261VH-3SS0BX-D11",
 
URL="#1HXF261VH-3SS0BX-D11",
 
URL="#1HXF261VH-3SS0BX-D11",
Line 202: Line 202:
 
height=0.32,
 
height=0.32,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1J2TTSH03-9498TK-12B" [id="1J2TTSH03-9498TK-12B",
 
"1J2TTSH03-9498TK-12B" [id="1J2TTSH03-9498TK-12B",
 
URL="#1J2TTSH03-9498TK-12B",
 
URL="#1J2TTSH03-9498TK-12B",
 
label="SIRT1",
 
label="SIRT1",
pos="24.14,-5.17!",
+
pos="19.57,-5.88!",
 
width=0.79,
 
width=0.79,
 
height=0.46,
 
height=0.46,
 
fontsize=12,
 
fontsize=12,
shape=oval, color="#ff9600ff"];
+
shape=circle, color="#ff9600ff"];
 
"1HXF3TW1Q-23JXDZC-FWS" [id="1HXF3TW1Q-23JXDZC-FWS",
 
"1HXF3TW1Q-23JXDZC-FWS" [id="1HXF3TW1Q-23JXDZC-FWS",
 
URL="#1HXF3TW1Q-23JXDZC-FWS",
 
URL="#1HXF3TW1Q-23JXDZC-FWS",
 
label="MAPK",
 
label="MAPK",
pos="9.46,-14.43!",
+
pos="5.71,-14.31!",
 
width=0.75,
 
width=0.75,
 
height=0.44,
 
height=0.44,
 
fontsize=12,
 
fontsize=12,
shape=oval, color="#ff0000ff"];
+
shape=circle, color="#ff0000ff"];
 
"1HXF15RQR-1KBC5BM-C6K" [id="1HXF15RQR-1KBC5BM-C6K",
 
"1HXF15RQR-1KBC5BM-C6K" [id="1HXF15RQR-1KBC5BM-C6K",
 
URL="#1HXF15RQR-1KBC5BM-C6K",
 
URL="#1HXF15RQR-1KBC5BM-C6K",
Line 226: Line 226:
 
height=0.67,
 
height=0.67,
 
fontsize=12,
 
fontsize=12,
shape=oval, color="#ffff99ff"];
+
shape=circle, color="#ffff00ff"];
 
"1HXF1P942-2BF86CX-CN0" [id="1HXF1P942-2BF86CX-CN0",
 
"1HXF1P942-2BF86CX-CN0" [id="1HXF1P942-2BF86CX-CN0",
 
URL="#1HXF1P942-2BF86CX-CN0",
 
URL="#1HXF1P942-2BF86CX-CN0",
 
label="Ubiquitination and proteasomal \nDegradation of Pin2/TRF1",
 
label="Ubiquitination and proteasomal \nDegradation of Pin2/TRF1",
pos="15.19,-13.31!",
+
pos="11.56,-13.22!",
 
width=2.83,
 
width=2.83,
 
height=0.51,
 
height=0.51,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXDX5L49-77W2CW-7HY" [id="1HXDX5L49-77W2CW-7HY",
 
"1HXDX5L49-77W2CW-7HY" [id="1HXDX5L49-77W2CW-7HY",
 
URL="#1HXDX5L49-77W2CW-7HY",
 
URL="#1HXDX5L49-77W2CW-7HY",
 
label="E3 ubiquitin \nLigase complex \nBRCA1/BARD1",
 
label="E3 ubiquitin \nLigase complex \nBRCA1/BARD1",
pos="8.49,-3.67!",
+
pos="9.29,-3.67!",
 
width=1.86,
 
width=1.86,
 
height=1.15,
 
height=1.15,
 
fontsize=12,
 
fontsize=12,
shape=oval, color="#ffff99ff"];
+
shape=circle, color="#ffff00ff"];
 
"1HXLLTPY9-V8MC72-153" [id="1HXLLTPY9-V8MC72-153",
 
"1HXLLTPY9-V8MC72-153" [id="1HXLLTPY9-V8MC72-153",
 
URL="#1HXLLTPY9-V8MC72-153",
 
URL="#1HXLLTPY9-V8MC72-153",
 
label="E3 ubiquitin ligase VHL",
 
label="E3 ubiquitin ligase VHL",
pos="20.86,-2!",
+
pos="19.5,-1.93!",
 
width=2.22,
 
width=2.22,
 
height=0.81,
 
height=0.81,
 
fontsize=12,
 
fontsize=12,
shape=oval, color="#ffff99ff"];
+
shape=circle, color="#ffff00ff"];
 
"1HXDXPP3Z-1K7XJS9-7ZK" [id="1HXDXPP3Z-1K7XJS9-7ZK",
 
"1HXDXPP3Z-1K7XJS9-7ZK" [id="1HXDXPP3Z-1K7XJS9-7ZK",
 
URL="#1HXDXPP3Z-1K7XJS9-7ZK",
 
URL="#1HXDXPP3Z-1K7XJS9-7ZK",
 
label="Р53",
 
label="Р53",
pos="1.26,-5.35!",
+
pos="2.07,-5.35!",
 
width=0.6,
 
width=0.6,
 
height=0.4,
 
height=0.4,
 
fontsize=12,
 
fontsize=12,
shape=oval, color="#808080ff"];
+
shape=circle, color="#ff00ffff"];
 
"1N9P55MTN-4H4V8F-1YRJ" [id="1N9P55MTN-4H4V8F-1YRJ",
 
"1N9P55MTN-4H4V8F-1YRJ" [id="1N9P55MTN-4H4V8F-1YRJ",
 
URL="#1N9P55MTN-4H4V8F-1YRJ",
 
URL="#1N9P55MTN-4H4V8F-1YRJ",
Line 266: Line 266:
 
height=0.67,
 
height=0.67,
 
fontsize=12,
 
fontsize=12,
shape=oval, color="#ffff99ff"];
+
shape=circle, color="#ffff00ff"];
 
"1NLC2KCGW-SKR5JN-38F" [id="1NLC2KCGW-SKR5JN-38F",
 
"1NLC2KCGW-SKR5JN-38F" [id="1NLC2KCGW-SKR5JN-38F",
 
URL="#1NLC2KCGW-SKR5JN-38F",
 
URL="#1NLC2KCGW-SKR5JN-38F",
 
label="ubiquitination",
 
label="ubiquitination",
pos="16.14,-7.42!",
+
pos="13.92,-8.08!",
 
width=2.64,
 
width=2.64,
 
height=0.72,
 
height=0.72,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXDYQ1VX-P0G5CN-8Y9" [id="1HXDYQ1VX-P0G5CN-8Y9",
 
"1HXDYQ1VX-P0G5CN-8Y9" [id="1HXDYQ1VX-P0G5CN-8Y9",
 
URL="#1HXDYQ1VX-P0G5CN-8Y9",
 
URL="#1HXDYQ1VX-P0G5CN-8Y9",
 
label="Complex 9-1-1",
 
label="Complex 9-1-1",
pos="6.07,-4.81!",
+
pos="6.88,-4.81!",
 
width=1.56,
 
width=1.56,
 
height=0.68,
 
height=0.68,
 
fontsize=12,
 
fontsize=12,
shape=oval, color="#ffff99ff"];
+
shape=circle, color="#ffff00ff"];
 
"1HXDY473R-160M3Z0-8C5" [id="1HXDY473R-160M3Z0-8C5",
 
"1HXDY473R-160M3Z0-8C5" [id="1HXDY473R-160M3Z0-8C5",
 
URL="#1HXDY473R-160M3Z0-8C5",
 
URL="#1HXDY473R-160M3Z0-8C5",
 
label="Transcription of \nproliferation genes",
 
label="Transcription of \nproliferation genes",
pos="11.5,-6.35!",
+
pos="12.03,-5.54!",
 
width=1.72,
 
width=1.72,
 
height=0.51,
 
height=0.51,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXDXX01M-SPR3HQ-82K" [id="1HXDXX01M-SPR3HQ-82K",
 
"1HXDXX01M-SPR3HQ-82K" [id="1HXDXX01M-SPR3HQ-82K",
 
URL="#1HXDXX01M-SPR3HQ-82K",
 
URL="#1HXDXX01M-SPR3HQ-82K",
 
label="Chk2 kinase",
 
label="Chk2 kinase",
pos="10.39,-2.67!",
+
pos="10.38,-2.28!",
 
width=1.31,
 
width=1.31,
 
height=0.6,
 
height=0.6,
 
fontsize=12,
 
fontsize=12,
shape=oval, color="#ff0000ff"];
+
shape=circle, color="#ff0000ff"];
 
"1N9P5YC6Y-WZZ1KZ-1Z1D" [id="1N9P5YC6Y-WZZ1KZ-1Z1D",
 
"1N9P5YC6Y-WZZ1KZ-1Z1D" [id="1N9P5YC6Y-WZZ1KZ-1Z1D",
 
URL="#1N9P5YC6Y-WZZ1KZ-1Z1D",
 
URL="#1N9P5YC6Y-WZZ1KZ-1Z1D",
 
label="XPC",
 
label="XPC",
pos="1.9,-7.18!",
+
pos="2.71,-7.18!",
 
width=0.49,
 
width=0.49,
 
height=0.28,
 
height=0.28,
Line 310: Line 310:
 
URL="#1HXDZTC5L-1T2SN4H-9N1",
 
URL="#1HXDZTC5L-1T2SN4H-9N1",
 
label="E3 ubiquitin ligase\nMKRN1",
 
label="E3 ubiquitin ligase\nMKRN1",
pos="6.26,-11.43!",
+
pos="19.5,-10.65!",
 
width=1.93,
 
width=1.93,
 
height=0.96,
 
height=0.96,
 
fontsize=12,
 
fontsize=12,
shape=oval, color="#ffff99ff"];
+
shape=circle, color="#ffff00ff"];
 
"1HXF413M8-1ZWD9C0-G37" [id="1HXF413M8-1ZWD9C0-G37",
 
"1HXF413M8-1ZWD9C0-G37" [id="1HXF413M8-1ZWD9C0-G37",
 
URL="#1HXF413M8-1ZWD9C0-G37",
 
URL="#1HXF413M8-1ZWD9C0-G37",
 
label="Ligand binding",
 
label="Ligand binding",
pos="10.58,-11.31!",
+
pos="6.83,-11.18!",
 
width=1.38,
 
width=1.38,
 
height=0.32,
 
height=0.32,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXF2PNF5-T888QY-F0C" [id="1HXF2PNF5-T888QY-F0C",
 
"1HXF2PNF5-T888QY-F0C" [id="1HXF2PNF5-T888QY-F0C",
 
URL="#1HXF2PNF5-T888QY-F0C",
 
URL="#1HXF2PNF5-T888QY-F0C",
 
label="Transition to \nCell cycle S-phase",
 
label="Transition to \nCell cycle S-phase",
pos="18.21,-14.33!",
+
pos="16.26,-14.14!",
 
width=1.68,
 
width=1.68,
 
height=0.51,
 
height=0.51,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXF16LX4-26J48HP-C7M" [id="1HXF16LX4-26J48HP-C7M",
 
"1HXF16LX4-26J48HP-C7M" [id="1HXF16LX4-26J48HP-C7M",
 
URL="#1HXF16LX4-26J48HP-C7M",
 
URL="#1HXF16LX4-26J48HP-C7M",
Line 338: Line 338:
 
height=0.51,
 
height=0.51,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1N9P5Y33L-1FNMXTX-1Z18" [id="1N9P5Y33L-1FNMXTX-1Z18",
 
"1N9P5Y33L-1FNMXTX-1Z18" [id="1N9P5Y33L-1FNMXTX-1Z18",
 
URL="#1N9P5Y33L-1FNMXTX-1Z18",
 
URL="#1N9P5Y33L-1FNMXTX-1Z18",
 
label="DDB2",
 
label="DDB2",
pos="2.83,-6.92!",
+
pos="3.64,-6.92!",
 
width=0.63,
 
width=0.63,
 
height=0.28,
 
height=0.28,
Line 350: Line 350:
 
URL="#1J1D8NGZC-20SQKFW-5M6",
 
URL="#1J1D8NGZC-20SQKFW-5M6",
 
label="Proteasome degradation of HIF-1a",
 
label="Proteasome degradation of HIF-1a",
pos="21.58,-14.61!",
+
pos="3.03,-14.26!",
 
width=3.06,
 
width=3.06,
 
height=0.32,
 
height=0.32,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXDX5TVJ-1TX6BB3-7JG" [id="1HXDX5TVJ-1TX6BB3-7JG",
 
"1HXDX5TVJ-1TX6BB3-7JG" [id="1HXDX5TVJ-1TX6BB3-7JG",
 
URL="#1HXDX5TVJ-1TX6BB3-7JG",
 
URL="#1HXDX5TVJ-1TX6BB3-7JG",
 
label="Histone H2AX \nMonoubiquitination",
 
label="Histone H2AX \nMonoubiquitination",
pos="8.51,-4.94!",
+
pos="9.32,-4.94!",
 
width=1.75,
 
width=1.75,
 
height=0.51,
 
height=0.51,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1J1D8GLS6-N6V8MY-5GP" [id="1J1D8GLS6-N6V8MY-5GP",
 
"1J1D8GLS6-N6V8MY-5GP" [id="1J1D8GLS6-N6V8MY-5GP",
 
URL="#1J1D8GLS6-N6V8MY-5GP",
 
URL="#1J1D8GLS6-N6V8MY-5GP",
 
label="Adducts with \ntranscription \nfactor Hif-1",
 
label="Adducts with \ntranscription \nfactor Hif-1",
pos="21.56,-11.86!",
+
pos="3,-11.51!",
 
width=1.4,
 
width=1.4,
 
height=0.79,
 
height=0.79,
 
fontsize=12,
 
fontsize=12,
shape=point, color="#000000ff"];
+
shape=hexagon, color="#00c8ffff"];
 
"1HXDY3B19-XD74WC-88N" [id="1HXDY3B19-XD74WC-88N",
 
"1HXDY3B19-XD74WC-88N" [id="1HXDY3B19-XD74WC-88N",
 
URL="#1HXDY3B19-XD74WC-88N",
 
URL="#1HXDY3B19-XD74WC-88N",
 
label="Binding of Rb",
 
label="Binding of Rb",
pos="11.46,-4.71!",
+
pos="11.99,-3.9!",
 
width=1.28,
 
width=1.28,
 
height=0.32,
 
height=0.32,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXF40D8M-1LTSYPY-G1J" [id="1HXF40D8M-1LTSYPY-G1J",
 
"1HXF40D8M-1LTSYPY-G1J" [id="1HXF40D8M-1LTSYPY-G1J",
 
URL="#1HXF40D8M-1LTSYPY-G1J",
 
URL="#1HXF40D8M-1LTSYPY-G1J",
 
label="Lysosomal degradation of EGF-R",
 
label="Lysosomal degradation of EGF-R",
pos="11.64,-14.49!",
+
pos="7.89,-14.36!",
 
width=2.89,
 
width=2.89,
 
height=0.32,
 
height=0.32,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXDXQ0P6-1FHWYSW-80J" [id="1HXDXQ0P6-1FHWYSW-80J",
 
"1HXDXQ0P6-1FHWYSW-80J" [id="1HXDXQ0P6-1FHWYSW-80J",
 
URL="#1HXDXQ0P6-1FHWYSW-80J",
 
URL="#1HXDXQ0P6-1FHWYSW-80J",
 
label="DNA repair genes",
 
label="DNA repair genes",
pos="1.25,-6.29!",
+
pos="2.06,-6.29!",
 
width=1.63,
 
width=1.63,
 
height=0.31,
 
height=0.31,
Line 398: Line 398:
 
URL="#1HXDY14S5-1LD6P1Q-86K",
 
URL="#1HXDY14S5-1LD6P1Q-86K",
 
label="Nucleoplasmin/B23",
 
label="Nucleoplasmin/B23",
pos="11.47,-3.69!",
+
pos="12,-2.89!",
 
width=1.9,
 
width=1.9,
 
height=0.81,
 
height=0.81,
 
fontsize=12,
 
fontsize=12,
shape=oval, color="#ffff99ff"];
+
shape=circle, color="#ffff00ff"];
 
"1HXDXBJY6-2013R63-7PX" [id="1HXDXBJY6-2013R63-7PX",
 
"1HXDXBJY6-2013R63-7PX" [id="1HXDXBJY6-2013R63-7PX",
 
URL="#1HXDXBJY6-2013R63-7PX",
 
URL="#1HXDXBJY6-2013R63-7PX",
 
label="ATM",
 
label="ATM",
pos="9.63,-1.65!",
+
pos="9.18,-1.4!",
 
width=0.64,
 
width=0.64,
 
height=0.42,
 
height=0.42,
 
fontsize=12,
 
fontsize=12,
shape=oval, color="#ff0000ff"];
+
shape=circle, color="#ff0000ff"];
 
"1HXF0TRRP-14KR8HB-BJS" [id="1HXF0TRRP-14KR8HB-BJS",
 
"1HXF0TRRP-14KR8HB-BJS" [id="1HXF0TRRP-14KR8HB-BJS",
 
URL="#1HXF0TRRP-14KR8HB-BJS",
 
URL="#1HXF0TRRP-14KR8HB-BJS",
 
label="E3 ubiquitin ligase MKRN1",
 
label="E3 ubiquitin ligase MKRN1",
pos="1.25,-3.61!",
+
pos="2.06,-3.61!",
 
width=2.49,
 
width=2.49,
 
height=0.86,
 
height=0.86,
 
fontsize=12,
 
fontsize=12,
shape=oval, color="#ffff99ff"];
+
shape=circle, color="#ffff00ff"];
 
"1HXDZXGR8-11H1VXM-9RL" [id="1HXDZXGR8-11H1VXM-9RL",
 
"1HXDZXGR8-11H1VXM-9RL" [id="1HXDZXGR8-11H1VXM-9RL",
 
URL="#1HXDZXGR8-11H1VXM-9RL",
 
URL="#1HXDZXGR8-11H1VXM-9RL",
 
label="Telomerase complex destruction",
 
label="Telomerase complex destruction",
pos="6.31,-13.88!",
+
pos="19.54,-13.1!",
 
width=2.88,
 
width=2.88,
 
height=0.32,
 
height=0.32,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1J2TTV0QY-1S75YF7-14X" [id="1J2TTV0QY-1S75YF7-14X",
 
"1J2TTV0QY-1S75YF7-14X" [id="1J2TTV0QY-1S75YF7-14X",
 
URL="#1J2TTV0QY-1S75YF7-14X",
 
URL="#1J2TTV0QY-1S75YF7-14X",
 
label="E3 ubiquitin ligase Skp2",
 
label="E3 ubiquitin ligase Skp2",
pos="24.14,-7.38!",
+
pos="19.57,-8.08!",
 
width=2.31,
 
width=2.31,
 
height=0.83,
 
height=0.83,
 
fontsize=12,
 
fontsize=12,
shape=oval, color="#ffff99ff"];
+
shape=circle, color="#ffff00ff"];
 
"1HXF423NB-1PLD05D-G51" [id="1HXF423NB-1PLD05D-G51",
 
"1HXF423NB-1PLD05D-G51" [id="1HXF423NB-1PLD05D-G51",
 
URL="#1HXF423NB-1PLD05D-G51",
 
URL="#1HXF423NB-1PLD05D-G51",
 
label="Cellular senescence",
 
label="Cellular senescence",
pos="11.6,-15.46!",
+
pos="7.9,-15.33!",
 
width=1.79,
 
width=1.79,
 
height=0.28,
 
height=0.28,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXF2DVY7-2C75KYW-DK4" [id="1HXF2DVY7-2C75KYW-DK4",
 
"1HXF2DVY7-2C75KYW-DK4" [id="1HXF2DVY7-2C75KYW-DK4",
 
URL="#1HXF2DVY7-2C75KYW-DK4",
 
URL="#1HXF2DVY7-2C75KYW-DK4",
 
label="Ubiquitination and proteasome \nDegradation of cyclin D1",
 
label="Ubiquitination and proteasome \nDegradation of cyclin D1",
pos="18.25,-13.31!",
+
pos="16.31,-13.11!",
 
width=2.79,
 
width=2.79,
 
height=0.51,
 
height=0.51,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXF23LXY-TG4R0T-CQW" [id="1HXF23LXY-TG4R0T-CQW",
 
"1HXF23LXY-TG4R0T-CQW" [id="1HXF23LXY-TG4R0T-CQW",
 
URL="#1HXF23LXY-TG4R0T-CQW",
 
URL="#1HXF23LXY-TG4R0T-CQW",
 
label="Telomere lengthening",
 
label="Telomere lengthening",
pos="15.19,-14.36!",
+
pos="11.56,-14.28!",
 
width=1.97,
 
width=1.97,
 
height=0.32,
 
height=0.32,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1J1D89CBX-J65J0B-59H" [id="1J1D89CBX-J65J0B-59H",
 
"1J1D89CBX-J65J0B-59H" [id="1J1D89CBX-J65J0B-59H",
 
URL="#1J1D89CBX-J65J0B-59H",
 
URL="#1J1D89CBX-J65J0B-59H",
 
label="High levels of glucose",
 
label="High levels of glucose",
pos="21.51,-9.63!",
+
pos="2.96,-9.28!",
 
width=2.08,
 
width=2.08,
 
height=0.43,
 
height=0.43,
Line 474: Line 474:
 
height=1,
 
height=1,
 
fontsize=12,
 
fontsize=12,
shape=oval, color="#ffff99ff"];
+
shape=circle, color="#ffff00ff"];
 
"1HXF24Q2K-K603LY-CSB" [id="1HXF24Q2K-K603LY-CSB",
 
"1HXF24Q2K-K603LY-CSB" [id="1HXF24Q2K-K603LY-CSB",
 
URL="#1HXF24Q2K-K603LY-CSB",
 
URL="#1HXF24Q2K-K603LY-CSB",
 
label="Telomere shortening",
 
label="Telomere shortening",
pos="6.31,-14.9!",
+
pos="19.54,-14.13!",
 
width=1.89,
 
width=1.89,
 
height=0.32,
 
height=0.32,
 
fontsize=12,
 
fontsize=12,
shape=rectangle, color="#808080ff"];
+
shape=rectangle, fontcolor="#008000ff", color="#808080ff"];
 
"1HXF1NHBS-1WFWH9C-CMN" [id="1HXF1NHBS-1WFWH9C-CMN",
 
"1HXF1NHBS-1WFWH9C-CMN" [id="1HXF1NHBS-1WFWH9C-CMN",
 
URL="#1HXF1NHBS-1WFWH9C-CMN",
 
URL="#1HXF1NHBS-1WFWH9C-CMN",
 
label="SCF Fbx4/alphaB\n-crystalline\nE3 ubiquitin \nligase complex",
 
label="SCF Fbx4/alphaB\n-crystalline\nE3 ubiquitin \nligase complex",
pos="16.6,-11.92!",
+
pos="14.28,-11.86!",
 
width=2.08,
 
width=2.08,
 
height=1.39,
 
height=1.39,
 
fontsize=12,
 
fontsize=12,
shape=oval, color="#ffff99ff"];
+
shape=circle, color="#ffff00ff"];
"1HXF3TF9N-2CNRBZM-FVR" -> "1HXF3TMQM-73NBC5-FW0" [color="#008000ff"]
+
"1HXF0TXZ0-2BJ3NZN-BJY" -> "1HXF0TRRP-14KR8HB-BJS" [arrowhead=tee, color="#ff0000ff"]
"1N9P66C3N-1KWKJKJ-1ZB3" -> "1HXDXX01M-SPR3HQ-82K" [color="#008000ff"]
+
"1NLC2KCGW-SKR5JN-38F" -> "1HXLLVYXK-YD59DQ-15R" [arrowhead=none, color="#000000ff"]
"1HXDY14S5-1LD6P1Q-86K" -> "1HXDY3B19-XD74WC-88N" [color="#008000ff"]
+
"1HXF3TW1Q-23JXDZC-FWS" -> "1HXF3W5MJ-D3H95R-FXG" [color="#008000ff"]
"1N9P5YC6Y-WZZ1KZ-1Z1D" -> "1HXDZ4FX8-1VG5BFM-92S" [color="#008000ff"]
+
"1HXDXPP3Z-1K7XJS9-7ZK" -> "1HXDXQ0P6-1FHWYSW-80J" [color="#008000ff"]
"1J2TTSH03-9498TK-12B" -> "1J2TTSY2L-Z3PR1X-12T" [color="#008000ff"]
+
"1HXF2DVY7-2C75KYW-DK4" -> "1HXF2PNF5-T888QY-F0C" [arrowhead=tee, color="#ff0000ff"]
 +
"1N9P66C3N-1KWKJKJ-1ZB3" -> "1HXDX5L49-77W2CW-7HY" [color="#008000ff"]
 +
"1HXF413M8-1ZWD9C0-G37" -> "1HXF3TF9N-2CNRBZM-FVR" [color="#008000ff"]
 +
"1NLC2KCGW-SKR5JN-38F" -> "1HXF1DZW9-1N3N3CF-CCH" [arrowhead=none, color="#000000ff"]
 +
"1HXDX70DD-C3RG63-7L2" -> "1HXDX8QW4-8CH6YX-7M9" [color="#008000ff"]
 +
"1HXDXQ0P6-1FHWYSW-80J" -> "1N9P5YMFF-15HT175-1Z1Z" [arrowhead=none, color="#000000ff"]
 +
"1HXDX5L49-77W2CW-7HY" -> "1HXDX5TVJ-1TX6BB3-7JG" [color="#008000ff"]
 +
"1HXDZVLBH-HRNZM1-9PT" -> "1HXDZXGR8-11H1VXM-9RL" [color="#008000ff"]
 
"1HXF3TF9N-2CNRBZM-FVR" -> "1HXF3XKMD-1MDXYWM-FZ1" [color="#008000ff"]
 
"1HXF3TF9N-2CNRBZM-FVR" -> "1HXF3XKMD-1MDXYWM-FZ1" [color="#008000ff"]
 +
"1HXDX5TVJ-1TX6BB3-7JG" -> "1HXDX70DD-C3RG63-7L2" [color="#008000ff"]
 +
"1J1D89CBX-J65J0B-59H" -> "1J1D8B0LY-77N6FX-5FN" [color="#0000ffff"]
 +
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"1N9P55MTN-4H4V8F-1YRJ" -> "1HXF16LX4-26J48HP-C7M" [color="#008000ff"]
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"1HXDY3N30-SXZ26V-89M" -> "1HXDY473R-160M3Z0-8C5" [color="#008000ff"]
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"1J1D8NGZC-20SQKFW-5M6" -> "1J1D8PQ19-MN9P7R-5P6" [color="#008000ff"]
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+
"1HXF0TXZ0-2BJ3NZN-BJY" -> "1HXF0TRRP-14KR8HB-BJS" [color="#ff0000ff"]
+
 
} </graphviz>(.//.)
 
} </graphviz>(.//.)
 
<!-- Categories list. You can add something if need. -->
 
<!-- Categories list. You can add something if need. -->
 
(.//.)<html><!--Pop-up for: Methylglyoxal !Pop-up-->
 
(.//.)<html><!--Pop-up for: Methylglyoxal !Pop-up-->
 
<div class="1J1D8B0LY-77N6FX-5FN" style="display:none;">
 
<div class="1J1D8B0LY-77N6FX-5FN" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Methylglyoxal</h3>
 
<h3>Methylglyoxal</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/14568006">PMID: 14568006</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/21124777">PMID: 21124777</a><br /></div>
 
</div>(...)<!--Pop-up for: E2F !Pop-up-->
 
</div>(...)<!--Pop-up for: E2F !Pop-up-->
 
<div class="1HXDY3N30-SXZ26V-89M" style="display:none;">
 
<div class="1HXDY3N30-SXZ26V-89M" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>E2F</h3>
 
<h3>E2F</h3>
<div class="links"> </div>
+
<div class="links"><a href="No links!"></a><br /><a href=" ">E2F</a><br /></div>
 
</div>(...)<!--Pop-up for: Ras !Pop-up-->
 
</div>(...)<!--Pop-up for: Ras !Pop-up-->
 
<div class="1HXF3TMQM-73NBC5-FW0" style="display:none;">
 
<div class="1HXF3TMQM-73NBC5-FW0" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Ras</h3>
 
<h3>Ras</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/21167805">PMID: 21167805</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/18604200">PMID: 18604200</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/19141677">PMID: 19141677</a><br /></div>
 
</div>(...)<!--Pop-up for: ATR !Pop-up-->
 
</div>(...)<!--Pop-up for: ATR !Pop-up-->
 
<div class="1N9P66C3N-1KWKJKJ-1ZB3" style="display:none;">
 
<div class="1N9P66C3N-1KWKJKJ-1ZB3" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>ATR</h3>
 
<h3>ATR</h3>
<div class="links"> </div>
+
<div class="links"></div>
 
</div>(...)<!--Pop-up for: Proliferation !Pop-up-->
 
</div>(...)<!--Pop-up for: Proliferation !Pop-up-->
 
<div class="1HXF3W5MJ-D3H95R-FXG" style="display:none;">
 
<div class="1HXF3W5MJ-D3H95R-FXG" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Proliferation</h3>
 
<h3>Proliferation</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/21167805">PMID: 21167805</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/18604200">PMID: 18604200</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/19141677">PMID: 19141677</a><br /></div>
 
</div>(...)<!--Pop-up for: Poliubiquitination of  Ubiquitin ligase CHIP by E3 !Pop-up-->
 
</div>(...)<!--Pop-up for: Poliubiquitination of  Ubiquitin ligase CHIP by E3 !Pop-up-->
 
<div class="1J1D8K6B5-17RSFTK-5JW" style="display:none;">
 
<div class="1J1D8K6B5-17RSFTK-5JW" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Poliubiquitination of  Ubiquitin ligase CHIP by E3</h3>
 
<h3>Poliubiquitination of  Ubiquitin ligase CHIP by E3</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/21124777">PMID: 21124777</a><br /></div>
 
</div>(...)<!--Pop-up for: Availability of damaged DNA For repair complexes !Pop-up-->
 
</div>(...)<!--Pop-up for: Availability of damaged DNA For repair complexes !Pop-up-->
 
<div class="1HXDX8QW4-8CH6YX-7M9" style="display:none;">
 
<div class="1HXDX8QW4-8CH6YX-7M9" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Availability of damaged DNA For repair complexes</h3>
 
<h3>Availability of damaged DNA For repair complexes</h3>
<div class="links"> </div>
+
<div class="links"><a href="No links!"></a><br /><a href=" ">Availability of damaged DNA For repair complexes</a><br /></div>
 
</div>(...)<!--Pop-up for: Transcription of adaptation  to hypoxia genes !Pop-up-->
 
</div>(...)<!--Pop-up for: Transcription of adaptation  to hypoxia genes !Pop-up-->
 
<div class="1HXLM05XC-1FSPCXC-17T" style="display:none;">
 
<div class="1HXLM05XC-1FSPCXC-17T" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Transcription of adaptation  to hypoxia genes</h3>
 
<h3>Transcription of adaptation  to hypoxia genes</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/11292862">PMID: 11292862</a><br /></div>
 
</div>(...)<!--Pop-up for: FOXO1 deacetylation !Pop-up-->
 
</div>(...)<!--Pop-up for: FOXO1 deacetylation !Pop-up-->
 
<div class="1J2TTSY2L-Z3PR1X-12T" style="display:none;">
 
<div class="1J2TTSY2L-Z3PR1X-12T" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>FOXO1 deacetylation</h3>
 
<h3>FOXO1 deacetylation</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/14976264">PMID: 14976264</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/15692560">PMID: 15692560</a><br /></div>
 
</div>(...)<!--Pop-up for: EGF-R !Pop-up-->
 
</div>(...)<!--Pop-up for: EGF-R !Pop-up-->
 
<div class="1HXF3TF9N-2CNRBZM-FVR" style="display:none;">
 
<div class="1HXF3TF9N-2CNRBZM-FVR" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>EGF-R</h3>
 
<h3>EGF-R</h3>
<div class="links"> </div>
+
<div class="links"></div>
 
</div>(...)<!--Pop-up for: Ubiquitination and proteasome  Degradation of p21 and p27 !Pop-up-->
 
</div>(...)<!--Pop-up for: Ubiquitination and proteasome  Degradation of p21 and p27 !Pop-up-->
 
<div class="1HXF1DZW9-1N3N3CF-CCH" style="display:none;">
 
<div class="1HXF1DZW9-1N3N3CF-CCH" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Ubiquitination and proteasome  Degradation of p21 and p27</h3>
 
<h3>Ubiquitination and proteasome  Degradation of p21 and p27</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/9311993">PMID: 9311993</a><br /></div>
 
</div>(...)<!--Pop-up for: E3 ubiquitin ligase complex  Rad6-Rad18 !Pop-up-->
 
</div>(...)<!--Pop-up for: E3 ubiquitin ligase complex  Rad6-Rad18 !Pop-up-->
 
<div class="1HXDYCP8F-2BZCX14-8VY" style="display:none;">
 
<div class="1HXDYCP8F-2BZCX14-8VY" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>E3 ubiquitin ligase complex  Rad6-Rad18</h3>
 
<h3>E3 ubiquitin ligase complex  Rad6-Rad18</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/16368276">PMID: 16368276</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/18485869">PMID: 18485869</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/19325626">PMID: 19325626</a><br /></div>
 
</div>(...)<!--Pop-up for: PCNA !Pop-up-->
 
</div>(...)<!--Pop-up for: PCNA !Pop-up-->
 
<div class="1HXDYPJ1C-RC1Z03-8X5" style="display:none;">
 
<div class="1HXDYPJ1C-RC1Z03-8X5" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>PCNA</h3>
 
<h3>PCNA</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/16368276">PMID: 16368276</a><br /></div>
 
</div>(...)<!--Pop-up for: Ubiquitination and proteasome  Degradation of HIF-1a !Pop-up-->
 
</div>(...)<!--Pop-up for: Ubiquitination and proteasome  Degradation of HIF-1a !Pop-up-->
 
<div class="1HXLLVYXK-YD59DQ-15R" style="display:none;">
 
<div class="1HXLLVYXK-YD59DQ-15R" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Ubiquitination and proteasome  Degradation of HIF-1a</h3>
 
<h3>Ubiquitination and proteasome  Degradation of HIF-1a</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/10973499">PMID: 10973499</a><br /></div>
 
</div>(...)<!--Pop-up for: DNA damage !Pop-up-->
 
</div>(...)<!--Pop-up for: DNA damage !Pop-up-->
 
<div class="1HXDXCP6L-1JPNVC5-7R3" style="display:none;">
 
<div class="1HXDXCP6L-1JPNVC5-7R3" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>DNA damage</h3>
 
<h3>DNA damage</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/21690091">PMID: 21690091</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/17210786">PMID: 17210786</a><br /></div>
 
</div>(...)<!--Pop-up for: Monoubiquitination by ligase Cbl !Pop-up-->
 
</div>(...)<!--Pop-up for: Monoubiquitination by ligase Cbl !Pop-up-->
 
<div class="1HXF3XKMD-1MDXYWM-FZ1" style="display:none;">
 
<div class="1HXF3XKMD-1MDXYWM-FZ1" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Monoubiquitination by ligase Cbl</h3>
 
<h3>Monoubiquitination by ligase Cbl</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/12218189">PMID: 12218189</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/10635327">PMID: 10635327</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/10531381">PMID: 10531381</a><br /></div>
 
</div>(...)<!--Pop-up for: ATP-dependent  Chromatin remodeling !Pop-up-->
 
</div>(...)<!--Pop-up for: ATP-dependent  Chromatin remodeling !Pop-up-->
 
<div class="1HXDX70DD-C3RG63-7L2" style="display:none;">
 
<div class="1HXDX70DD-C3RG63-7L2" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>ATP-dependent  Chromatin remodeling</h3>
 
<h3>ATP-dependent  Chromatin remodeling</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/22289628">PMID: 22289628</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/17306844">PMID: 17306844</a><br /></div>
 
</div>(...)<!--Pop-up for: Ubiquitination and proteasome  Degradation of FOXO1 !Pop-up-->
 
</div>(...)<!--Pop-up for: Ubiquitination and proteasome  Degradation of FOXO1 !Pop-up-->
 
<div class="1J2TTVWV5-1XB3QXN-15M" style="display:none;">
 
<div class="1J2TTVWV5-1XB3QXN-15M" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Ubiquitination and proteasome  Degradation of FOXO1</h3>
 
<h3>Ubiquitination and proteasome  Degradation of FOXO1</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/15692560">PMID: 15692560</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/21238503">PMID: 21238503</a><br /></div>
 
</div>(...)<!--Pop-up for: DNA repair !Pop-up-->
 
</div>(...)<!--Pop-up for: DNA repair !Pop-up-->
 
<div class="1HXDZ4FX8-1VG5BFM-92S" style="display:none;">
 
<div class="1HXDZ4FX8-1VG5BFM-92S" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>DNA repair</h3>
 
<h3>DNA repair</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/19376751">PMID: 19376751</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/12967652">PMID: 12967652</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/19325626">PMID: 19325626</a><br /></div>
 
</div>(...)<!--Pop-up for: Normoxia !Pop-up-->
 
</div>(...)<!--Pop-up for: Normoxia !Pop-up-->
 
<div class="1HXLLS50M-1PPGMX8-11F" style="display:none;">
 
<div class="1HXLLS50M-1PPGMX8-11F" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Normoxia</h3>
 
<h3>Normoxia</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/12006670">PMID: 12006670</a><br /></div>
 
</div>(...)<!--Pop-up for: PCNA !Pop-up-->
 
</div>(...)<!--Pop-up for: PCNA !Pop-up-->
 
<div class="1N9P5YMFF-15HT175-1Z1Z" style="display:none;">
 
<div class="1N9P5YMFF-15HT175-1Z1Z" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>PCNA</h3>
 
<h3>PCNA</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/16368276">PMID: 16368276</a><br /></div>
 
</div>(...)<!--Pop-up for: ARF !Pop-up-->
 
</div>(...)<!--Pop-up for: ARF !Pop-up-->
 
<div class="1HXF0TXZ0-2BJ3NZN-BJY" style="display:none;">
 
<div class="1HXF0TXZ0-2BJ3NZN-BJY" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>ARF</h3>
 
<h3>ARF</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/17210786">PMID: 17210786</a><br /></div>
 
</div>(...)<!--Pop-up for: Disturbance of tissue resistance to hypoxia !Pop-up-->
 
</div>(...)<!--Pop-up for: Disturbance of tissue resistance to hypoxia !Pop-up-->
 
<div class="1J1D8PQ19-MN9P7R-5P6" style="display:none;">
 
<div class="1J1D8PQ19-MN9P7R-5P6" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Disturbance of tissue resistance to hypoxia</h3>
 
<h3>Disturbance of tissue resistance to hypoxia</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/10749844">PMID: 10749844</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/16517406">PMID: 16517406</a><br /></div>
 
</div>(...)<!--Pop-up for: Ubiquitination and proteasomal  Degradation of hTERT !Pop-up-->
 
</div>(...)<!--Pop-up for: Ubiquitination and proteasomal  Degradation of hTERT !Pop-up-->
 
<div class="1HXDZVLBH-HRNZM1-9PT" style="display:none;">
 
<div class="1HXDZVLBH-HRNZM1-9PT" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Ubiquitination and proteasomal  Degradation of hTERT</h3>
 
<h3>Ubiquitination and proteasomal  Degradation of hTERT</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/15805468">PMID: 15805468</a><br /></div>
 
</div>(...)<!--Pop-up for: Cell proliferation !Pop-up-->
 
</div>(...)<!--Pop-up for: Cell proliferation !Pop-up-->
 
<div class="1HXF261VH-3SS0BX-D11" style="display:none;">
 
<div class="1HXF261VH-3SS0BX-D11" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Cell proliferation</h3>
 
<h3>Cell proliferation</h3>
<div class="links"> </div>
+
<div class="links"><a href="No links!"></a><br /><a href=" ">Cell proliferation</a><br /></div>
 
</div>(...)<!--Pop-up for: SIRT1 !Pop-up-->
 
</div>(...)<!--Pop-up for: SIRT1 !Pop-up-->
 
<div class="1J2TTSH03-9498TK-12B" style="display:none;">
 
<div class="1J2TTSH03-9498TK-12B" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>SIRT1</h3>
 
<h3>SIRT1</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/14976264">PMID: 14976264</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/15692560">PMID: 15692560</a><br /></div>
 
</div>(...)<!--Pop-up for: MAPK !Pop-up-->
 
</div>(...)<!--Pop-up for: MAPK !Pop-up-->
 
<div class="1HXF3TW1Q-23JXDZC-FWS" style="display:none;">
 
<div class="1HXF3TW1Q-23JXDZC-FWS" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>MAPK</h3>
 
<h3>MAPK</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/21167805">PMID: 21167805</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/18604200">PMID: 18604200</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/19141677">PMID: 19141677</a><br /></div>
 
</div>(...)<!--Pop-up for: Cyclin E/Cdk2 !Pop-up-->
 
</div>(...)<!--Pop-up for: Cyclin E/Cdk2 !Pop-up-->
 
<div class="1HXF15RQR-1KBC5BM-C6K" style="display:none;">
 
<div class="1HXF15RQR-1KBC5BM-C6K" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Cyclin E/Cdk2</h3>
 
<h3>Cyclin E/Cdk2</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/8033213">PMID: 8033213</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/9192873">PMID: 9192873</a><br /></div>
 
</div>(...)<!--Pop-up for: Ubiquitination and proteasomal  Degradation of Pin2/TRF1 !Pop-up-->
 
</div>(...)<!--Pop-up for: Ubiquitination and proteasomal  Degradation of Pin2/TRF1 !Pop-up-->
 
<div class="1HXF1P942-2BF86CX-CN0" style="display:none;">
 
<div class="1HXF1P942-2BF86CX-CN0" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Ubiquitination and proteasomal  Degradation of Pin2/TRF1</h3>
 
<h3>Ubiquitination and proteasomal  Degradation of Pin2/TRF1</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/20159592">PMID: 20159592</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/11375976">PMID: 11375976</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/16275645">PMID: 16275645</a><br /></div>
 
</div>(...)<!--Pop-up for: E3 ubiquitin  Ligase complex  BRCA1/BARD1 !Pop-up-->
 
</div>(...)<!--Pop-up for: E3 ubiquitin  Ligase complex  BRCA1/BARD1 !Pop-up-->
 
<div class="1HXDX5L49-77W2CW-7HY" style="display:none;">
 
<div class="1HXDX5L49-77W2CW-7HY" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>E3 ubiquitin  Ligase complex  BRCA1/BARD1</h3>
 
<h3>E3 ubiquitin  Ligase complex  BRCA1/BARD1</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/21690091">PMID: 21690091</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/19015238">PMID: 19015238</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/11790560">PMID: 11790560</a><br /></div>
 
</div>(...)<!--Pop-up for: E3 ubiquitin ligase VHL !Pop-up-->
 
</div>(...)<!--Pop-up for: E3 ubiquitin ligase VHL !Pop-up-->
 
<div class="1HXLLTPY9-V8MC72-153" style="display:none;">
 
<div class="1HXLLTPY9-V8MC72-153" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>E3 ubiquitin ligase VHL</h3>
 
<h3>E3 ubiquitin ligase VHL</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/10421634">PMID: 10421634</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/10973499">PMID: 10973499</a><br /></div>
 
</div>(...)<!--Pop-up for: Р53 !Pop-up-->
 
</div>(...)<!--Pop-up for: Р53 !Pop-up-->
 
<div class="1HXDXPP3Z-1K7XJS9-7ZK" style="display:none;">
 
<div class="1HXDXPP3Z-1K7XJS9-7ZK" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Р53</h3>
 
<h3>Р53</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/19536131">PMID: 19536131</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/23742843">PMID: 23742843</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/12967652">PMID: 12967652</a><br /></div>
 
</div>(...)<!--Pop-up for: Cyclin A/Cdk2 !Pop-up-->
 
</div>(...)<!--Pop-up for: Cyclin A/Cdk2 !Pop-up-->
 
<div class="1N9P55MTN-4H4V8F-1YRJ" style="display:none;">
 
<div class="1N9P55MTN-4H4V8F-1YRJ" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Cyclin A/Cdk2</h3>
 
<h3>Cyclin A/Cdk2</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/9325318">PMID: 9325318</a><br /></div>
 
</div>(...)<!--Pop-up for: ubiquitination !Pop-up-->
 
</div>(...)<!--Pop-up for: ubiquitination !Pop-up-->
 
<div class="1NLC2KCGW-SKR5JN-38F" style="display:none;">
 
<div class="1NLC2KCGW-SKR5JN-38F" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>ubiquitination</h3>
 
<h3>ubiquitination</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/18374642">PMID: 18374642</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/11395416">PMID: 11395416</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/10906270">PMID: 10906270</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/10662664">PMID: 10662664</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/19754430">PMID: 19754430</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/18533226">PMID: 18533226</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/16246514">PMID: 16246514</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/20886764">PMID: 20886764</a><br /></div>
 
</div>(...)<!--Pop-up for: Complex 9-1-1 !Pop-up-->
 
</div>(...)<!--Pop-up for: Complex 9-1-1 !Pop-up-->
 
<div class="1HXDYQ1VX-P0G5CN-8Y9" style="display:none;">
 
<div class="1HXDYQ1VX-P0G5CN-8Y9" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Complex 9-1-1</h3>
 
<h3>Complex 9-1-1</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/18485869">PMID: 18485869</a><br /></div>
 
</div>(...)<!--Pop-up for: Transcription of  proliferation genes !Pop-up-->
 
</div>(...)<!--Pop-up for: Transcription of  proliferation genes !Pop-up-->
 
<div class="1HXDY473R-160M3Z0-8C5" style="display:none;">
 
<div class="1HXDY473R-160M3Z0-8C5" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Transcription of  proliferation genes</h3>
 
<h3>Transcription of  proliferation genes</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/18024471">PMID: 18024471</a><br /></div>
 
</div>(...)<!--Pop-up for: Chk2 kinase !Pop-up-->
 
</div>(...)<!--Pop-up for: Chk2 kinase !Pop-up-->
 
<div class="1HXDXX01M-SPR3HQ-82K" style="display:none;">
 
<div class="1HXDXX01M-SPR3HQ-82K" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Chk2 kinase</h3>
 
<h3>Chk2 kinase</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/9836640">PMID: 9836640</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/10531348">PMID: 10531348</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/11431331">PMID: 11431331</a><br /></div>
 
</div>(...)<!--Pop-up for: XPC !Pop-up-->
 
</div>(...)<!--Pop-up for: XPC !Pop-up-->
 
<div class="1N9P5YC6Y-WZZ1KZ-1Z1D" style="display:none;">
 
<div class="1N9P5YC6Y-WZZ1KZ-1Z1D" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>XPC</h3>
 
<h3>XPC</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/15107491">PMID: 15107491</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/12177305">PMID: 12177305</a><br /></div>
 
</div>(...)<!--Pop-up for: E3 ubiquitin ligase MKRN1 !Pop-up-->
 
</div>(...)<!--Pop-up for: E3 ubiquitin ligase MKRN1 !Pop-up-->
 
<div class="1HXDZTC5L-1T2SN4H-9N1" style="display:none;">
 
<div class="1HXDZTC5L-1T2SN4H-9N1" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>E3 ubiquitin ligase MKRN1</h3>
 
<h3>E3 ubiquitin ligase MKRN1</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/19536131">PMID: 19536131</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/15805468">PMID: 15805468</a><br /></div>
 
</div>(...)<!--Pop-up for: Ligand binding !Pop-up-->
 
</div>(...)<!--Pop-up for: Ligand binding !Pop-up-->
 
<div class="1HXF413M8-1ZWD9C0-G37" style="display:none;">
 
<div class="1HXF413M8-1ZWD9C0-G37" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Ligand binding</h3>
 
<h3>Ligand binding</h3>
<div class="links"> </div>
+
<div class="links"><a href="No links!"></a><br /><a href=" ">Ligand binding</a><br /></div>
 
</div>(...)<!--Pop-up for: Transition to  Cell cycle S-phase !Pop-up-->
 
</div>(...)<!--Pop-up for: Transition to  Cell cycle S-phase !Pop-up-->
 
<div class="1HXF2PNF5-T888QY-F0C" style="display:none;">
 
<div class="1HXF2PNF5-T888QY-F0C" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Transition to  Cell cycle S-phase</h3>
 
<h3>Transition to  Cell cycle S-phase</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/8114703">PMID: 8114703</a><br /></div>
 
</div>(...)<!--Pop-up for: Phosphorylation of inhibitor of cyclin-dependent  Kinases p21 and p27 !Pop-up-->
 
</div>(...)<!--Pop-up for: Phosphorylation of inhibitor of cyclin-dependent  Kinases p21 and p27 !Pop-up-->
 
<div class="1HXF16LX4-26J48HP-C7M" style="display:none;">
 
<div class="1HXF16LX4-26J48HP-C7M" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Phosphorylation of inhibitor of cyclin-dependent  Kinases p21 and p27</h3>
 
<h3>Phosphorylation of inhibitor of cyclin-dependent  Kinases p21 and p27</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/8033213">PMID: 8033213</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/9311993">PMID: 9311993</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/8242751">PMID: 8242751</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/7626805">PMID: 7626805</a><br /></div>
 
</div>(...)<!--Pop-up for: DDB2 !Pop-up-->
 
</div>(...)<!--Pop-up for: DDB2 !Pop-up-->
 
<div class="1N9P5Y33L-1FNMXTX-1Z18" style="display:none;">
 
<div class="1N9P5Y33L-1FNMXTX-1Z18" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>DDB2</h3>
 
<h3>DDB2</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/16951172">PMID: 16951172</a><br /></div>
 
</div>(...)<!--Pop-up for: Proteasome degradation of HIF-1a !Pop-up-->
 
</div>(...)<!--Pop-up for: Proteasome degradation of HIF-1a !Pop-up-->
 
<div class="1J1D8NGZC-20SQKFW-5M6" style="display:none;">
 
<div class="1J1D8NGZC-20SQKFW-5M6" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Proteasome degradation of HIF-1a</h3>
 
<h3>Proteasome degradation of HIF-1a</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/21124777">PMID: 21124777</a><br /></div>
 
</div>(...)<!--Pop-up for: Histone H2AX  Monoubiquitination !Pop-up-->
 
</div>(...)<!--Pop-up for: Histone H2AX  Monoubiquitination !Pop-up-->
 
<div class="1HXDX5TVJ-1TX6BB3-7JG" style="display:none;">
 
<div class="1HXDX5TVJ-1TX6BB3-7JG" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Histone H2AX  Monoubiquitination</h3>
 
<h3>Histone H2AX  Monoubiquitination</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/21690091">PMID: 21690091</a><br /></div>
 
</div>(...)<!--Pop-up for: Adducts with  transcription  factor Hif-1 !Pop-up-->
 
</div>(...)<!--Pop-up for: Adducts with  transcription  factor Hif-1 !Pop-up-->
 
<div class="1J1D8GLS6-N6V8MY-5GP" style="display:none;">
 
<div class="1J1D8GLS6-N6V8MY-5GP" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Adducts with  transcription  factor Hif-1</h3>
 
<h3>Adducts with  transcription  factor Hif-1</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/21124777">PMID: 21124777</a><br /></div>
 
</div>(...)<!--Pop-up for: Binding of Rb !Pop-up-->
 
</div>(...)<!--Pop-up for: Binding of Rb !Pop-up-->
 
<div class="1HXDY3B19-XD74WC-88N" style="display:none;">
 
<div class="1HXDY3B19-XD74WC-88N" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Binding of Rb</h3>
 
<h3>Binding of Rb</h3>
<div class="links"> </div>
+
<div class="links"><a href="No links!"></a><br /><a href=" ">Binding of Rb</a><br /></div>
 
</div>(...)<!--Pop-up for: Lysosomal degradation of EGF-R !Pop-up-->
 
</div>(...)<!--Pop-up for: Lysosomal degradation of EGF-R !Pop-up-->
 
<div class="1HXF40D8M-1LTSYPY-G1J" style="display:none;">
 
<div class="1HXF40D8M-1LTSYPY-G1J" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Lysosomal degradation of EGF-R</h3>
 
<h3>Lysosomal degradation of EGF-R</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/14641021">PMID: 14641021</a><br /></div>
 
</div>(...)<!--Pop-up for: DNA repair genes !Pop-up-->
 
</div>(...)<!--Pop-up for: DNA repair genes !Pop-up-->
 
<div class="1HXDXQ0P6-1FHWYSW-80J" style="display:none;">
 
<div class="1HXDXQ0P6-1FHWYSW-80J" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>DNA repair genes</h3>
 
<h3>DNA repair genes</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/19376751">PMID: 19376751</a><br /></div>
 
</div>(...)<!--Pop-up for: Nucleoplasmin/B23 !Pop-up-->
 
</div>(...)<!--Pop-up for: Nucleoplasmin/B23 !Pop-up-->
 
<div class="1HXDY14S5-1LD6P1Q-86K" style="display:none;">
 
<div class="1HXDY14S5-1LD6P1Q-86K" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Nucleoplasmin/B23</h3>
 
<h3>Nucleoplasmin/B23</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/11602260">PMID: 11602260</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/18024471">PMID: 18024471</a><br /></div>
 
</div>(...)<!--Pop-up for: ATM !Pop-up-->
 
</div>(...)<!--Pop-up for: ATM !Pop-up-->
 
<div class="1HXDXBJY6-2013R63-7PX" style="display:none;">
 
<div class="1HXDXBJY6-2013R63-7PX" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>ATM</h3>
 
<h3>ATM</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/21690091">PMID: 21690091</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/9836640">PMID: 9836640</a><br /></div>
 
</div>(...)<!--Pop-up for: E3 ubiquitin ligase MKRN1 !Pop-up-->
 
</div>(...)<!--Pop-up for: E3 ubiquitin ligase MKRN1 !Pop-up-->
 
<div class="1HXF0TRRP-14KR8HB-BJS" style="display:none;">
 
<div class="1HXF0TRRP-14KR8HB-BJS" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>E3 ubiquitin ligase MKRN1</h3>
 
<h3>E3 ubiquitin ligase MKRN1</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/19536131">PMID: 19536131</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/15805468">PMID: 15805468</a><br /></div>
 
</div>(...)<!--Pop-up for: Telomerase complex destruction !Pop-up-->
 
</div>(...)<!--Pop-up for: Telomerase complex destruction !Pop-up-->
 
<div class="1HXDZXGR8-11H1VXM-9RL" style="display:none;">
 
<div class="1HXDZXGR8-11H1VXM-9RL" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Telomerase complex destruction</h3>
 
<h3>Telomerase complex destruction</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/15805468">PMID: 15805468</a><br /></div>
 
</div>(...)<!--Pop-up for: E3 ubiquitin ligase Skp2 !Pop-up-->
 
</div>(...)<!--Pop-up for: E3 ubiquitin ligase Skp2 !Pop-up-->
 
<div class="1J2TTV0QY-1S75YF7-14X" style="display:none;">
 
<div class="1J2TTV0QY-1S75YF7-14X" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>E3 ubiquitin ligase Skp2</h3>
 
<h3>E3 ubiquitin ligase Skp2</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/15668399">PMID: 15668399</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/21238503">PMID: 21238503</a><br /></div>
 
</div>(...)<!--Pop-up for: Cellular senescence !Pop-up-->
 
</div>(...)<!--Pop-up for: Cellular senescence !Pop-up-->
 
<div class="1HXF423NB-1PLD05D-G51" style="display:none;">
 
<div class="1HXF423NB-1PLD05D-G51" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Cellular senescence</h3>
 
<h3>Cellular senescence</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/21852385">PMID: 21852385</a><br /></div>
 
</div>(...)<!--Pop-up for: Ubiquitination and proteasome  Degradation of cyclin D1 !Pop-up-->
 
</div>(...)<!--Pop-up for: Ubiquitination and proteasome  Degradation of cyclin D1 !Pop-up-->
 
<div class="1HXF2DVY7-2C75KYW-DK4" style="display:none;">
 
<div class="1HXF2DVY7-2C75KYW-DK4" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Ubiquitination and proteasome  Degradation of cyclin D1</h3>
 
<h3>Ubiquitination and proteasome  Degradation of cyclin D1</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/17224055">PMID: 17224055</a><br /></div>
 
</div>(...)<!--Pop-up for: Telomere lengthening !Pop-up-->
 
</div>(...)<!--Pop-up for: Telomere lengthening !Pop-up-->
 
<div class="1HXF23LXY-TG4R0T-CQW" style="display:none;">
 
<div class="1HXF23LXY-TG4R0T-CQW" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Telomere lengthening</h3>
 
<h3>Telomere lengthening</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/16275645">PMID: 16275645</a><br /></div>
 
</div>(...)<!--Pop-up for: High levels of glucose !Pop-up-->
 
</div>(...)<!--Pop-up for: High levels of glucose !Pop-up-->
 
<div class="1J1D89CBX-J65J0B-59H" style="display:none;">
 
<div class="1J1D89CBX-J65J0B-59H" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>High levels of glucose</h3>
 
<h3>High levels of glucose</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/14568006">PMID: 14568006</a><br /></div>
 
</div>(...)<!--Pop-up for:  E3 ubiquitin ligase SCF-Skp2 !Pop-up-->
 
</div>(...)<!--Pop-up for:  E3 ubiquitin ligase SCF-Skp2 !Pop-up-->
 
<div class="1HXF1C9SL-1NY06WB-CBC" style="display:none;">
 
<div class="1HXF1C9SL-1NY06WB-CBC" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3> E3 ubiquitin ligase SCF-Skp2</h3>
 
<h3> E3 ubiquitin ligase SCF-Skp2</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/10375532">PMID: 10375532</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/12730199">PMID: 12730199</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/15340381">PMID: 15340381</a><br /></div>
 
</div>(...)<!--Pop-up for: Telomere shortening !Pop-up-->
 
</div>(...)<!--Pop-up for: Telomere shortening !Pop-up-->
 
<div class="1HXF24Q2K-K603LY-CSB" style="display:none;">
 
<div class="1HXF24Q2K-K603LY-CSB" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>Telomere shortening</h3>
 
<h3>Telomere shortening</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/15805468">PMID: 15805468</a><br /></div>
 
</div>(...)<!--Pop-up for: SCF Fbx4/alphaB -crystalline E3 ubiquitin  ligase complex !Pop-up-->
 
</div>(...)<!--Pop-up for: SCF Fbx4/alphaB -crystalline E3 ubiquitin  ligase complex !Pop-up-->
 
<div class="1HXF1NHBS-1WFWH9C-CMN" style="display:none;">
 
<div class="1HXF1NHBS-1WFWH9C-CMN" style="display:none;">
 +
 +
 +
 +
 +
  
  
  
 
<h3>SCF Fbx4/alphaB -crystalline E3 ubiquitin  ligase complex</h3>
 
<h3>SCF Fbx4/alphaB -crystalline E3 ubiquitin  ligase complex</h3>
<div class="links"> </div>
+
<div class="links"><a href="http://www.ncbi.nlm.nih.gov/pubmed/18818515">PMID: 18818515</a><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/17224055">PMID: 17224055</a><br /></div>
</div>(.//.)(.//.)<!-- Do not edit!  -->
+
</div>(.//.)<h1>Role of ubiquitination</h1>
 +
 
 +
<p>The conserved 76-residue polypeptide ubiquitin fulfills essential functions in eukaryotes through its covalent conjugation to other intracellular proteins. Ubiquitin is first activated by an ATP-dependent reaction involving a ubiquitin activating enzyme (E1), followed by its conjugation via a thioester bond to a cysteine residue in a ubiquitin-conjugating enzyme (E2). In the final enzymatic step, ubiquitin is transferred from the E2 enzyme to a target lysine residue in a particular substrate protein by a ubiquitin-protein isopeptide ligase (E3). E3 enzymes are often characterized by the presence of a C3HC4 (RING) finger motif, which binds zinc and is required for ubiquitin ligase activity. Substrates can be mono- or polyubiquitinated; whereas polyubiquitination targets proteins for degradation via the 26S proteasome, monoubiquitination generally acts as a tag that marks the substrate protein to signal for a particular function. One well-characterized example of this process is the monoubiquitination of histones H2A and H2B. The three-step ubiquitination mechanism initiates all known ubiquitination reactions, independent of whether the substrate-bound ubiquitin(s) will signal proteasomal proteolysis, endocytosis, or some other fate. </p>
 +
<p>Because ubiquitination has several possible consequences, the manner in which a covalent ubiquitin signal is interpreted must depend in some cases on additional factors, such as the subcellular localization of the substrate or the number and topology of the substrate-conjugated ubiquitins. For example, substrates destined for proteasomes are usually conjugated to a polyubiquitin chain in which successive ubiquitins are linked by K48-G76 isopeptide bonds, whereas chains linked through K63-G76 bonds have been strongly implicated in nonproteolytic signaling. Nonetheless, specificity in signaling by ubiquitin arises primarily at the stage of ubiquitination. The role of ubiquitin in cell cycle progression, for example, is readily explained by the periodic ubiquitination of positive and negative regulators, leading to the appropriately timed degradation of these factors by proteasomes.</p>
 +
<p>The organization of the enzymatic conjugating cascade is hierarchical: There is one E1; a significant but limited number of E2s, each of which may serve several E3s; and a much larger number of E3s (many which remain to be identified). Each E3 recognizes a set of substrates that share one or more ubiquitination signals, and cooperates with one or a few E2s. </p>
 +
<p>Ubiquitination signals on target proteins can be genetically programmed, or can be acquired by phosphorylation, by binding to an adapter protein, or by protein damage due to fragmentation, oxidation, or aging. The ubiquitin system was first identified as a pathway for the degradation of damaged proteins and that is the other major role it plays. Proteins damaged by oxidation or mutation or that misfold or mislocalize are good substrates for this system. Abnormal proteins in the cytoplasm are bound to the microtubule network and localized to the centrosome along with many of the enzymes of the pathway.22, 23 Misfolded proteins in the ER are shuttled back to the cytoplasm by retrograde transport and ubiquitinated and degraded there. </p>(.//.)<!-- Do not edit!  -->
 
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Latest revision as of 09:26, 2 August 2015

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Role of ubiquitination

The conserved 76-residue polypeptide ubiquitin fulfills essential functions in eukaryotes through its covalent conjugation to other intracellular proteins. Ubiquitin is first activated by an ATP-dependent reaction involving a ubiquitin activating enzyme (E1), followed by its conjugation via a thioester bond to a cysteine residue in a ubiquitin-conjugating enzyme (E2). In the final enzymatic step, ubiquitin is transferred from the E2 enzyme to a target lysine residue in a particular substrate protein by a ubiquitin-protein isopeptide ligase (E3). E3 enzymes are often characterized by the presence of a C3HC4 (RING) finger motif, which binds zinc and is required for ubiquitin ligase activity. Substrates can be mono- or polyubiquitinated; whereas polyubiquitination targets proteins for degradation via the 26S proteasome, monoubiquitination generally acts as a tag that marks the substrate protein to signal for a particular function. One well-characterized example of this process is the monoubiquitination of histones H2A and H2B. The three-step ubiquitination mechanism initiates all known ubiquitination reactions, independent of whether the substrate-bound ubiquitin(s) will signal proteasomal proteolysis, endocytosis, or some other fate.

Because ubiquitination has several possible consequences, the manner in which a covalent ubiquitin signal is interpreted must depend in some cases on additional factors, such as the subcellular localization of the substrate or the number and topology of the substrate-conjugated ubiquitins. For example, substrates destined for proteasomes are usually conjugated to a polyubiquitin chain in which successive ubiquitins are linked by K48-G76 isopeptide bonds, whereas chains linked through K63-G76 bonds have been strongly implicated in nonproteolytic signaling. Nonetheless, specificity in signaling by ubiquitin arises primarily at the stage of ubiquitination. The role of ubiquitin in cell cycle progression, for example, is readily explained by the periodic ubiquitination of positive and negative regulators, leading to the appropriately timed degradation of these factors by proteasomes.

The organization of the enzymatic conjugating cascade is hierarchical: There is one E1; a significant but limited number of E2s, each of which may serve several E3s; and a much larger number of E3s (many which remain to be identified). Each E3 recognizes a set of substrates that share one or more ubiquitination signals, and cooperates with one or a few E2s.

Ubiquitination signals on target proteins can be genetically programmed, or can be acquired by phosphorylation, by binding to an adapter protein, or by protein damage due to fragmentation, oxidation, or aging. The ubiquitin system was first identified as a pathway for the degradation of damaged proteins and that is the other major role it plays. Proteins damaged by oxidation or mutation or that misfold or mislocalize are good substrates for this system. Abnormal proteins in the cytoplasm are bound to the microtubule network and localized to the centrosome along with many of the enzymes of the pathway.22, 23 Misfolded proteins in the ER are shuttled back to the cytoplasm by retrograde transport and ubiquitinated and degraded there.