Ras signalling linked to the cell-cycle machinery by the retinoblastoma protein

被引:319
作者
Peeper, DS
Upton, TM
Ladha, MH
Neuman, E
Zalvide, J
Bernards, R
DeCaprio, JA
Ewen, ME
机构
[1] DANA FARBER CANC INST,BOSTON,MA 02115
[2] HARVARD UNIV,SCH MED,BOSTON,MA 02115
[3] NETHERLANDS CANC INST,DEPT MOL CARCINOGENESIS,NL-1066 CX AMSTERDAM,NETHERLANDS
关键词
D O I
10.1038/386177a0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The Ras proto-oncogene is a central component of mitogenic signal-transduction pathways, and is essential for cells both to leave a quiescent state (G0) and to pass through the G1/S transition of the cell cycle(1-6). The mechanism by which Ras signalling regulates cell-cycle progression is unclear, however. Here we report that the retinoblastoma tumour-suppressor protein (Rb), a regulator of G1 exit(7), functionally Links pas to passage through the G1 phase. Inactivation of Ras in cycling cells-caused a decline in cyclin D1 protein levels, accumulation of the hypophosphorylated, growth-suppressive form of Rb, and G1 arrest. When Rb was disrupted either genetically or biochemically, cells failed to arrest in G1 following Ras inactivation. In contrast, inactivation of Ras in quiescent cells prevented growth-factor induction of both immediate-early gene transcription and exit from G0 in an Rb-independent manner. These data suggest that Rb is an essential G1-specific mediator that links Ras-dependent mitogenic signalling to cell-cycle regulation.
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页码:177 / 181
页数:5
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