Cks1 promotion of S phase entry and proliferation is independent of p27Kip1 suppression.

Abstract:

:Cks1 is an activator of the SCF(Skp2) ubiquitin ligase complex that targets the cell cycle inhibitor p27(Kip1) for degradation. The loss of Cks1 results in p27(Kip1) accumulation and decreased proliferation and inhibits tumorigenesis. We identify here a function of Cks1 in mammalian cell cycle regulation that is independent of p27(Kip1). Specifically, Cks1(-/-); p27(Kip1-/-) mouse embryonic fibroblasts retain defects in the G(1)-S phase transition that are coupled with decreased Cdk2-associated kinase activity and defects in proliferation that are associated with Cks1 loss. Furthermore, concomitant loss of Cks1 does not rescue the tumor suppressor function of p27(Kip1) that is manifest in various organs of p27(Kip1-/-) mice. In contrast, defects in mitotic entry and premature senescence manifest in Cks1(-/-) cells are p27(Kip1) dependent. Collectively, these findings establish p27(Kip1)-independent functions of Cks1 in regulating the G(1)-S transition.

journal_name

Mol Cell Biol

authors

Hoellein A,Graf S,Bassermann F,Schoeffmann S,Platz U,Hölzlwimmer G,Kröger M,Peschel C,Oostendorp R,Quintanilla-Fend L,Keller U

doi

10.1128/MCB.06771-11

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

2416-27

issue

13

eissn

0270-7306

issn

1098-5549

pii

MCB.06771-11

journal_volume

32

pub_type

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