The F-box protein SKP2 binds to the phosphorylated threonine 380 in cyclin E and regulates ubiquitin-dependent degradation of cyclin E.
The F-box protein SKP2 binds to the phosphorylated threonine 380 in cyclin E and regulates ubiquitin-dependent degradation of cyclin E.
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DOI：
10.1006/bbrc.2001.4442
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发表时间：
2001-03
影响因子：
3.1
通讯作者：
Kun-Huei Yeh;T. Kondo;Jianyu Zheng;L. Tsvetkov;Jenny Blair;Hui Zhang
中科院分区：
文献类型：
--
作者：
Kun-Huei Yeh;T. Kondo;Jianyu Zheng;L. Tsvetkov;Jenny Blair;Hui Zhang
细胞周期蛋白E是进入S期所必需的。随后的泛素依赖性细胞周期蛋白E的降解有助于S期的有序进展。研究表明，细胞周期蛋白E中苏氨酸380（Thr 380）的磷酸化为其泛素依赖性蛋白水解提供了信号。我们报告，SKP 2，一个F-盒蛋白和SCF（SKP 2）泛素E3连接酶复合物的底物靶向成分，介导细胞周期蛋白E降解。在体外，SKP 2特异性地与含有磷酸化Thr 380的细胞周期蛋白E肽相互作用，但不与同源非磷酸化肽相互作用。在体内，SKP 2的表达诱导细胞周期蛋白E多聚泛素化和降解。Thr 380转化为nonphosphorylatable氨基酸导致细胞周期蛋白E对SKP 2的显著抗性。CDK抑制剂p27（Kip 1）的存在也阻止了SKP 2依赖的细胞周期蛋白E的降解。我们的研究结果表明，SKP 2调节细胞周期蛋白E的稳定性，从而有助于控制S期进展。
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. It 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 SCF(SKP2) 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. In 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.