Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation
- PMID: 14536078
- DOI: 10.1016/s1097-2765(03)00287-9
Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation
Abstract
Autophosphorylation-triggered ubiquitination has been proposed to be the major pathway regulating cyclin E protein abundance: phosphorylation of cyclin E on T380 by its associated CDK allows binding to the receptor subunit, Fbw7, of the SCFFbw7 ubiquitin ligase. We have tested this model in vivo and found it to be an inadequate representation of the pathways that regulate cyclin E degradation. We show that assembly of cyclin E into cyclin E-Cdk2 complexes is required in vivo for turnover by the Fbw7 pathway; that Cdk2 activity is required for cyclin E turnover in vivo because it phosphorylates S384; that phosphorylation of T380 in vivo does not require Cdk2 and is mediated primarily by GSK3; and that two additional phosphorylation sites, T62 and S372, are also required for turnover. Thus, cyclin E turnover is controlled by multiple biological inputs and cannot be understood in terms of autophosphorylation alone.
Comment in
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Jun: stealth, stability, and transformation.Mol Cell. 2005 Aug 19;19(4):432-3. doi: 10.1016/j.molcel.2005.08.004. Mol Cell. 2005. PMID: 16109367 Review.
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