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J Biol Chem, Vol. 273, Issue 30, 18812-18818, July 24, 1998
,
From the The Rho family of GTPases plays an important and
diverse role in reorganization of the actin cytoskeleton,
transcriptional regulation, and multiple aspects of cell growth. Our
study has examined their potential links to the cell cycle machinery.
We find that constitutively active mutants of Rac and Cdc42, but not
Rho, are potent inducers of E2F transcriptional activity in NIH 3T3
fibroblasts. Furthermore, activated Rac and Cdc42, but again not Rho,
are capable of inducing cyclin D1 accumulation and pRB
hyperphosphorylation in serum-deprived cells, outlining one route
leading to enhanced E2F-mediated transcription. The inhibitory effect
of the cyclin-dependent kinase inhibitors, p16ink4,
p21cip1, and p27cip on
Rac/Cdc42-mediated E2F transcription corroborates a role for pRB family
members and their functional inactivation by
cyclin-dependent kinases in generating E2F activity. While
the up-regulation of E2F transcriptional activity by Rac or Cdc42, not
Rho, suffices for entry into S phase and DNA synthesis in Rat-1 R12
cells, this is clearly not the case in NIH 3T3, where additional
requirements must exist.
Department of Molecular and Cellular
Biology, University of Copenhagen, Øster Farimagsgade 2A, DK 1353, Copenhagen K, Denmark and § Division of Cancer Biology,
Danish Cancer Society, Strandboulevarden 49, DK 2100, Copenhagen Ø, Denmark
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