The F-box protein SKP2 binds to the phosphorylated threonine 380 in cyclin E and regulates ubiquitin-dependent degradation of cyclin E

被引:53
作者
Yeh, KH [1 ]
Kondo, T [1 ]
Zheng, JY [1 ]
Tsvetkov, LM [1 ]
Blair, J [1 ]
Zhang, H [1 ]
机构
[1] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA
关键词
cell cycle; cyclin E; CDK2; p27(Kip1); SKP2; SCF; SKP1; CUL-1; ubiquitin-dependent proteolysis; S phase;
D O I
10.1006/bbrc.2001.4442
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cyclin E is required for S phase entry. The subsequent ubiquitin-dependent degradation of cyclin E contributes to an orderly progression of the S phase. Tt has been shown that phosphorylation of threonine 380 (Thr380) in cyclin E provides a signal for its ubiquitin-dependent proteolysis. We report that SKP2, an F-box protein and a substrate-targeting component of the SCFSKP2 ubiquitin E3 ligase complex, mediates cyclin E degradation. In vitro, SKP2 specifically interacted with the cyclin E peptide containing the phosphorylated-Thr380 but not with a cognate nonphosphorylated peptide. fn vivo expression of SKP2 induced cyclin E polyubiquitination and degradation. Conversion of Thr380 into nonphosphorylatable amino acids caused significant resistance of cyclin E to SKP2. The presence of the CDK. inhibitor p27(Kip1) also prevented the SKP2-dependent degradation of cyclin E. Our findings suggest that SKP2 regulates cyclin E stability, thus contributing to the control of S phase progression. (C) 2001 Academic Press.
引用
收藏
页码:884 / 890
页数:7
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