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

Abstract:

: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. 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, functionally links Ras 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.

journal_name

Nature

journal_title

Nature

authors

Peeper DS,Upton TM,Ladha MH,Neuman E,Zalvide J,Bernards R,DeCaprio JA,Ewen ME

doi

10.1038/386177a0

subject

Has Abstract

pub_date

1997-03-13 00:00:00

pages

177-81

issue

6621

eissn

0028-0836

issn

1476-4687

journal_volume

386

pub_type

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