| Cks1 promotion of S phase entry and proliferation is independent of p27Kip1 suppression. | |
| | |
MedLine Citation:
|
PMID: 22508990 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
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: 2013-02-20 |
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 |
Affiliation:
|
Medical Department III, Technische Universität München, Munich, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals CDC2-CDC28 Kinases / deficiency, genetics, metabolism* Cell Proliferation Cells, Cultured Cyclin-Dependent Kinase Inhibitor p27 / deficiency, genetics, metabolism* Cyclin-Dependent Kinases / metabolism Female Fibroblasts / metabolism G1 Phase Cell Cycle Checkpoints / physiology G2 Phase Cell Cycle Checkpoints / physiology Male Mice Mice, 129 Strain Mice, Inbred C57BL Mice, Knockout Phenotype S Phase Cell Cycle Checkpoints / physiology* S-Phase Kinase-Associated Proteins / metabolism |
| Chemical | |
Reg. No./Substance:
|
0/Cdkn1b protein, mouse; 0/S-Phase Kinase-Associated Proteins; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 2.7.11.22/CDC2-CDC28 Kinases; EC 2.7.11.22/Cks1 protein, mouse; EC 2.7.11.22/Cyclin-Dependent Kinases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The arginine attenuator peptide interferes with the ribosome peptidyl transferase center.
Next Document: The PRINTS database: a fine-grained protein sequence annotation and analysis resource--its status in...