Cell cycle regulation of the mammalian CDK activator RINGO/Speedy A
Cell cycle regulation of the mammalian CDK activator RINGO/Speedy A
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DOI：
10.1016/j.febslet.2009.07.028
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发表时间：
2009-09-03
期刊：
影响因子：
3.5
通讯作者：
Nebreda, Angel R.
中科院分区：
文献类型：
--
作者：
Dinarina, Ana;Santamaria, Patricia G.;Nebreda, Angel R.
细胞周期进程受细胞周期蛋白依赖性激酶（CDK）的调节，其激活需要称为细胞周期蛋白的调节亚基的结合。RINGO/Speedy A是一种哺乳动物蛋白，与细胞周期蛋白没有氨基酸序列同源性，但可以激活CDK。在这里，我们表明，RINGO/快速A是一种高度不稳定的蛋白质，其表达和磷酸化在细胞周期中定期调节。RINGO/Speedy A被蛋白酶体降解，该过程涉及泛素连接酶SCFSkp2。稳定的RINGO/Speedy A形式的过表达导致在有丝分裂的晚期积累高水平的RINGO/Speedy A，其干扰胞质分裂和染色体解凝聚。我们的数据表明RINGO/Speedy A的严格调控对体细胞周期很重要。结构总结：MINT-7226413：RINGO A（uniprotkb：Q5MJ70）物理相互作用（MI：0914）与泛素（uniprotkb：P62988）通过抗诱饵免疫共沉淀（MI：0006）MINT-7226431，MINT-7226448：RINGO A（uniprotkb：Q5MJ70）物理相互作用（MI：0914）与Skp2（uniprotkb：Q13309）通过抗标签共免疫沉淀（MI：0007）（C）2009欧洲生物化学学会联合会。由Elsevier B出版。V.保留所有权利。
Cell cycle progression is regulated by cyclin-dependent kinases (CDKs), whose activation requires the binding of regulatory subunits named cyclins. RINGO/Speedy A is a mammalian protein that has no amino acid sequence homology with cyclins but can activate CDKs. Here we show that RINGO/Speedy A is a highly unstable protein whose expression and phosphorylation are periodically regulated during the cell cycle. RINGO/Speedy A is degraded by the proteasome and the process involves the ubiquitin ligase SCFSkp2. Overexpression of a stabilized RINGO/Speedy A form results in the accumulation of high levels of RINGO/Speedy A at late stages of mitosis, which interfere with cytokinesis and chromosome decondensation. Our data show that tight regulation of RINGO/Speedy A is important for the somatic cell cycle.Structured summary:MINT-7226413: RINGO A (uniprotkb: Q5MJ70) physically interacts (MI: 0914) with Ubiquitin ( uniprotkb: P62988) by anti bait coimmunoprecipitation ( MI: 0006) MINT-7226431, MINT-7226448: RINGO A ( uniprotkb: Q5MJ70) physically interacts ( MI: 0914) with Skp2 ( uniprotkb: Q13309) by anti tag coimmunoprecipitation ( MI: 0007) (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.