Cks1 Promotion of S Phase Entry and Proliferation Is Independent of p27Kip1 Suppression
| Autor: | Christian Peschel, Stephanie Schoeffmann, Ulrich Platz, Florian Bassermann, Steffi Graf, Gabriele Hölzlwimmer, Monika Kröger, Robert A.J. Oostendorp, Ulrich Keller, Alexander Hoellein, Leticia Quintanilla-Fend |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Mice 129 Strain Biology medicine.disease_cause Mice CDC2-CDC28 Kinases medicine SKP2 Animals Kinase activity S-Phase Kinase-Associated Proteins Molecular Biology Mitosis Cells Cultured Cell Proliferation Mice Knockout Activator (genetics) Articles Cell Biology Fibroblasts Cell cycle G1 Phase Cell Cycle Checkpoints Embryonic stem cell Cyclin-Dependent Kinases Cell biology G2 Phase Cell Cycle Checkpoints Mice Inbred C57BL Phenotype Ubiquitin ligase complex S Phase Cell Cycle Checkpoints Female Carcinogenesis Cyclin-Dependent Kinase Inhibitor p27 |
| Zdroj: | Molecular and Cellular Biology. 32:2416-2427 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.06771-11 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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