The Ets transcription factor GABP is required for cell-cycle progression.

Abstract:

:The transition from cellular quiescence (G0) into S phase is regulated by the mitogenic-activation of D-type cyclins and cyclin-dependent kinases (Cdks), the sequestration of the Cdk inhibitors (CDKIs), p21 and p27, and the hyperphosphorylation of Rb with release of E2F transcription factors. However, fibroblasts that lack all D-type cyclins can still undergo serum-induced proliferation and key E2F targets are expressed at stable levels despite cyclical Rb-E2F activity. Here, we show that serum induces expression of the Ets transcription factor, Gabpalpha, and that its ectopic expression induces quiescent cells to re-enter the cell cycle. Genetic disruption of Gabpalpha prevents entry into S phase, and selectively reduces expression of genes that are required for DNA synthesis and degradation of CDKIs, yet does not alter expression of D-type cyclins, Cdks, Rb or E2Fs. Thus, GABP is necessary and sufficient for re-entry into the cell cycle and it regulates a pathway that is distinct from that of D-type cyclins and CDKs.

journal_name

Nat Cell Biol

journal_title

Nature cell biology

authors

Yang ZF,Mott S,Rosmarin AG

doi

10.1038/ncb1548

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

339-46

issue

3

eissn

1465-7392

issn

1476-4679

pii

ncb1548

journal_volume

9

pub_type

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