DNA-PKcs negatively regulates cyclin B1 protein stability through facilitating its ubiquitination mediated by Cdh1-APC/C pathway

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

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1026-1035
Number of pages10
JournalInternational Journal of Biological Sciences
Volume11
Issue number9
DOIs
StatePublished - Jul 14 2015

Keywords

  • Cyclin B1
  • DNA-PKcs

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Shang, Z. F., Tan, W., Liu, X. D., Yu, L., Li, B., Li, M., Song, M., Wang, Y., Xiao, B. B., Zhong, C. G., Guan, H., & Zhou, P. K. (2015). DNA-PKcs negatively regulates cyclin B1 protein stability through facilitating its ubiquitination mediated by Cdh1-APC/C pathway. International Journal of Biological Sciences, 11(9), 1026-1035. https://doi.org/10.7150/ijbs.12443