期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 288, 期 18, 页码 12615-12626出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M112.435701
关键词
-
资金
- Ministry of Health, Labour, and Welfare of Japan
- Japan Society for the Promotion of Science
- Ministry of Education, Culture, Sports, Science, and Technology, Japan
- National Institute of Biomedical Innovation (NIBIO), Japan
- Ministry of Health, Labour, and Welfare, Japan
- Grants-in-Aid for Scientific Research [24680038, 23650199] Funding Source: KAKEN
Dysregulation of cell proliferation and the cell cycle are associated with various diseases, such as cancer. Cyclin-dependent kinases (CDKs) play central roles in cell proliferation and the cell cycle. Ubiquitin C-terminal hydrolase L1 (UCH-L1) is expressed in a restricted range of tissues, including the brain and numerous types of cancer. However, the molecular functions of UCH-L1 remain elusive. In this study, we found that UCH-L1 physically interacts with CDK1, CDK4, and CDK5, enhancing their kinase activity. Using several mutants of UCH-L1, we showed that this enhancement is dependent upon interaction levels between UCH-L1 and CDKs but is independent of the known ubiquitin-related functions of UCH-L1. Gain-and loss-of-function studies revealed that UCH-L1 enhances proliferation of multiple cell types, including human cancer cells. Inhibition of the interaction between UCH-L1 and cell cycle-associated CDK resulted in the abolishment of UCH-L1-induced enhancement of cell proliferation. RNA interference of UCH-L1 reduced the growth of human xenograft tumors in mice. We concluded that UCH-L1 is a novel regulator of the kinase activities of CDKs. We believe that our findings from this study will significantly contribute to our understanding of cell cycle-associated diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据