Zeng-Fu Shang, Wei Tan, Xiao-Dan Liu, Lan Yu, Bing Li, Ming Li, Man Song, Yu Wang, Bei-Bei Xiao, Cai-Gao Zhong, Hua Guan, Ping-Kun Zhou
International journal of biological sciences 2015The 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.
Zeng-Fu Shang, Wei Tan, Xiao-Dan Liu, Lan Yu, Bing Li, Ming Li, Man Song, Yu Wang, Bei-Bei Xiao, Cai-Gao Zhong, Hua Guan, Ping-Kun Zhou. DNA-PKcs Negatively Regulates Cyclin B1 Protein Stability through Facilitating Its Ubiquitination Mediated by Cdh1-APC/C Pathway. International journal of biological sciences. 2015;11(9):1026-35
PMID: 26221070
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