DNA-PKcs Negatively Regulates Cyclin B1 Protein Stability Through Facilitating Its Ubiquitination Mediated by Cdh1-APC/C Pathway

Overview

Journal Int J Biol Sci

Specialty Biology

Date 2015 Jul 30

PMID 26221070

Citations 11

Authors

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

Affiliations

Soon will be listed here.

Abstract

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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