Document Detail

Cks1 promotion of S phase entry and proliferation is independent of p27Kip1 suppression.
MedLine Citation:
PMID:  22508990     Owner:  NLM     Status:  MEDLINE    
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.
Alexander Hoellein; Steffi Graf; Florian Bassermann; Stephanie Schoeffmann; Ulrich Platz; Gabriele Hölzlwimmer; Monika Kröger; Christian Peschel; Robert Oostendorp; Leticia Quintanilla-Fend; Ulrich Keller
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-16
Journal Detail:
Title:  Molecular and cellular biology     Volume:  32     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-06-11     Completed Date:  2012-09-06     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2416-27     Citation Subset:  IM    
Medical Department III, Technische Universität München, Munich, Germany.
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MeSH Terms
CDC2-CDC28 Kinases / deficiency,  genetics,  metabolism*
Cell Proliferation
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p27 / deficiency,  genetics,  metabolism*
Cyclin-Dependent Kinases / metabolism
Fibroblasts / metabolism
G1 Phase Cell Cycle Checkpoints / physiology
G2 Phase Cell Cycle Checkpoints / physiology
Mice, 129 Strain
Mice, Inbred C57BL
Mice, Knockout
S Phase Cell Cycle Checkpoints / physiology*
S-Phase Kinase-Associated Proteins / metabolism
Reg. No./Substance:
0/Cdkn1b protein, mouse; 0/S-Phase Kinase-Associated Proteins; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC Kinases; EC protein, mouse; EC Kinases

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