Constitutive Turnover of Cyclin E by Cul3 Maintains Quiescence.
From: Department of Molecular Biology, Cell Biology and Biochemistry and Center for Genomics and Proteomics, Brown University, 70 Ship Street, Box G-E337, Providence, RI 02903, USA.
Molecular and cellular biology
- Publish Date: May 2007
- ISSN: 0270-7306
- Volume: 27
- Issue: 10
- Pages: 3651-66
- Medium: Print
- Language: English
- Citation (JAMA): McEvoy Justina D, Kossatz Uta, Malek Nisar, et al. Constitutive Turnover of Cyclin E by Cul3 Maintains Quiescence.. Mol. Cell. Biol. May 2007;27:3651-66
Abstract
Two distinct pathways for the degradation of mammalian cyclin E have previously been described. One pathway is induced by cyclin E phosphorylation and is dependent on the Cul1/Fbw7-based E3 ligase. The other pathway is dependent on the Cul3-based E3 ligase, but the mechanistic details of this pathway have yet to be elucidated. To establish the role of Cul3 in the degradation of cyclin E in vivo, we created a conditional knockout of the Cul3 gene in mice. Interestingly, the biallelic loss of Cul3 in primary fibroblasts derived from these mice results in increased cyclin E expression and reduced cell viability, paralleling the loss of Cul3 protein expression. Cell cycle analysis of viable, Cul3 hypomorphic cells shows that decreasing the levels of Cul3 increases both cyclin E protein levels and the number of cells in S phase. In order to examine the role of Cul3 in an in vivo setting, we determined the effect of deletion of the Cul3 gene in liver. This gene deletion resulted in a dramatic increase in cyclin E levels as well as an increase in cell size and ploidy. The results we report here show that the constitutive degradation pathway for cyclin E that is regulated by the Cul3-based E3 ligase is essential to maintain quiescence in mammalian cells.
Mesh Headings (Keywords): Animals, Cell Cycle, Cell Cycle Proteins, Cell Survival, Cells, Cultured, Cullin Proteins, Cyclin E, Fibroblasts, Hepatocytes, Mice, Mice, Knockout, Phenotype
Check for Full Text / PubMed Unique Identifier (PMID): 17339333
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