Identification and characterization of CAC1 as a novel CDK2-associated cullin
Identification and characterization of CAC1 as a novel CDK2-associated cullin
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DOI：
10.4161/cc.8.21.9955
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发表时间：
2009-11-01
期刊：
影响因子：
4.3
通讯作者：
Yin, Yuxin
中科院分区：
文献类型：
--
作者：
Kong, Ying;Nan, Kejun;Yin, Yuxin
细胞周期进程受到细胞周期蛋白和细胞周期蛋白依赖性激酶（CDK）的严格控制。CDK 2在调节细胞周期进程中起着至关重要的作用，但CDK 2是如何调节的仍然不完全清楚。在这项研究中，我们报告了调节CDK 2活性的新基因CAC 1的鉴定和表征。该基因的开放阅读框序列编码含有Cullin结构域的369个氨基酸的蛋白质，并且该蛋白质与CDK 2物理相关。因此，我们将其命名为Cdk相关Cullin 1或CAC 1。CAC 1在癌组织和癌细胞系中高度表达。有趣的是，CAC 1以细胞周期依赖性方式表达，并且其表达在G1晚期至S期高。通过RNAi敲低CAC 1抑制细胞增殖并诱导G（1）/S阻滞。由于CAC 1与CDK 2相互作用，并促进CDK 2蛋白的激酶活性，我们认为CAC 1是一种新的细胞周期相关蛋白，能够促进细胞增殖。我们的数据提供了对CDK 2调节机制和癌症细胞周期进展的分子基础的深入了解。
Cell cycle progression is tightly controlled by cyclins and cyclin-dependent kinases (CDKs). CDK2 plays a crucial role in regulating cell cycle progression, but how CDK2 is regulated is still incompletely understood. In this study, we report the identification and characterization of a novel gene CAC1 that regulates CDK2 activity. The open reading frame sequence of this gene encodes a protein of 369 amino acids which contains a Cullin domain, and this protein is physically associated with CDK2. As such, we have designated it Cdk-Associated Cullin1, or CAC1. CAC1 is highly expressed in cancer tissues and cancer cell lines. Interestingly, CAC1 is expressed in a cell cycle-dependent manner and its expression is high in late G 1 to S phase. Knockdown of CAC1 by RNAi inhibits cell proliferation and induces G(1)/S arrest. Since CAC1 interacts with CDK2 and promotes the kinase activity of CDK2 protein, we propose that CAC1 is a novel cell cycle associated protein capable of promoting cell proliferation. Our data provide insight into the mechanism by which CDK2 is regulated and the molecular basis of cell cycle progression in cancer.