生物
细胞周期蛋白依赖激酶
细胞周期蛋白
细胞周期蛋白D
细胞周期蛋白A2
细胞周期
细胞周期蛋白
分子生物学
细胞生物学
细胞周期蛋白D1
细胞周期蛋白B
细胞周期蛋白
异位表达
生物化学
基因
作者
Heita Ozawa,Satoshi Ashizawa,Masanori Naito,Masatomo Yanagihara,Naomi Ohnishi,Tatsuya Maeda,Yoichi Matsuda,Yoshimasa Jo,Hideaki Higashi,Akira Kakita,Masanori Hatakeyama
出处
期刊:Oncogene
[Springer Nature]
日期:2004-07-05
卷期号:23 (39): 6590-6602
被引量:15
标识
DOI:10.1038/sj.onc.1207884
摘要
The eukaryotic cell cycle is regulated by sequential activation and inactivation of cyclin-cyclin-dependent kinase (Cdk) complexes. In this work, we screened human cDNAs that can rescue yeast Saccharomyces cerevisiae from lethality caused by ectopic expression of human cyclin E and isolated a cDNA encoding ESXR1, a paired-like homeodomain-containing protein with a unique C-terminal proline-rich repeat region. In adult tissues, ESXR1 is primarily expressed in the testis. We demonstrate that ESXR1 prevents degradation of ubiquitinated cyclins in human cells. Accordingly, elevation of ESXR1 level results in accumulation of cyclin A and cyclin B1 and thereby provokes M-phase arrest. In human cells, the 65-kDa full-length ESXR1 protein is capable of proteolytically processing into N-terminal 45-kDa and C-terminal 20-kDa fragments. The C-terminal fragment, containing a proline-rich repeat region, is localized to the cytoplasm and displays the ability to inhibit cyclin degradation. In contrast, the N-terminal fragment, containing a paired-like homeodomain, is localized exclusively in the nucleus, suggesting that it plays a role in transcription. Our results indicate that proteolytic processing of ESXR1 plays a role in concerted regulation of the cell cycle and transcription in human cells.
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