期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
卷 11, 期 9, 页码 1026-1035出版社
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.12443
关键词
Cyclin B1; DNA-PKcs
资金
- National Key Basic Research Program of MOST, China (973 Program) [2015CB910601]
- China National Science Foundation [81472919]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
The catalytic subunit of DNA-dependent protein kinase ( DNA-PKcs) is a critical component of the non-homologous end-joining pathway of DNA double-stranded break repair. DNA-PKcs has also been shown recently functioning in mitotic regulation. Here, we report that DNA-PKcs negatively regulates the stability of Cyclin B1 protein through facilitating its ubiquitination mediated by Cdh1/E 3 ubiquitin ligase APC/C pathway. Loss of DNA-PKcs causes abnormal accumulation of Cyclin B1 protein. Cyclin B1 degradation is delayed in DNA-PKcs-deficient cells as result of attenuated ubiquitination. The impact of DNA-PKcs on Cyclin B1 stability relies on its kinase activity. Our study further reveals that DNA-PKcs interacts with APC/C core component APC2 and its co-activator Cdh1. The destruction of Cdh1 is accelerated in the absence of DNA-PKcs. Moreover, overexpression of exogenous Cdh1 can reverse the increase of Cyclin B1 protein in DNA-PKcs-deficient cells. Thus, DNA-PKcs, in addition to its direct role in DNA damage repair, functions in mitotic progression at least partially through regulating the stability of Cyclin B1 protein.
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