Constitutive turnover of cyclin E by Cul3 maintains quiescence.

Constitutive turnover of cyclin E by Cul3 maintains quiescence. Research Abstract Details 

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Constitutive turnover of cyclin E by Cul3 maintains quiescence. Abstract Text:

Justina D McEvoy,Uta Kossatz,Nisar Malek,Jeffrey D Singer,

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.

Constitutive turnover of cyclin E by Cul3 maintains quiescence. Publishing Authors By Initials

JD McEvoy,U Kossatz,N Malek,JD Singer,

For similar genetic phenomena: phenotype research abstracts see: genetic phenomena: phenotype research

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Constitutive turnover of cyclin E by Cul3 maintains quiescence. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular and cellular biology

VOLUME: 27

Page Numbers: 3651-66

Journal Abbreviation:

ISSN: 0270-7306

DAY: 5

MONTH: 03

YEAR: 2007

Constitutive turnover of cyclin E by Cul3 maintains quiescence. Information

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LANGUAGE: eng

NlmUniqueID: 8109087

Constitutive turnover of cyclin E by Cul3 maintains quiescence. Keywords Mesh Terms:

KEYWORDS: Phenotype

MESH TERMS: physiology

Chemical & Substance for Abstract: Constitutive turnover of cyclin E by Cul3 maintains quiescence. Information

Substance Name: Cyclin E

Registry Number: 0

Grant and Affiliation Information for Constitutive turnover of cyclin E by Cul3 maintains quiescence.

AFFILIATION: 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.

Country: United States

AGENCY: United States NCRR

GRANT: P20 RR 015578

ACRONYM: RR

MEDLINETA: Mol Cell Biol

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