期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 112, 期 12, 页码 3856-3862出版社
WILEY-BLACKWELL
DOI: 10.1002/jcb.23317
关键词
USP7; HLTF; PCNA; UBIQUITINATION; DEUBIQUITINATION; DNA DAMAGE
资金
- Min Hang District Science and Technology Committee [2009MHZ063]
- Shanghai Jiao-Tong University School of Medicine [BXJ201009]
Human helicase-like transcription factor (HLTF) is a functional homologue of yeast Rad5 that regulates error-free replication through DNA lesions. HLTF promotes the Lys-63-linked polyubiquitination of proliferating cell nuclear antigen (PCNA) that is required for maintaining genomic stability. Here, we identified the deubiquitylating enzyme ubiquitin-specific protease 7 (USP7) as a novel regulator of HLTF stability. We found that USP7 interacted with and stabilized HLTF after genotoxic stress. Furthermore, USP7 mediated deubiquitination significantly prolonged the half-life of HLTF, which in turn increased PCNA polyubiquitination. More intriguingly, silencing of USP7 rendered A549 cells highly sensitive to DNA damage and over-expression of HLTF attenuated this sensitivity. Thus, our results delineate a previously unknown USP7-HLTF-PCNA molecular network controlling DNA damage response. J. Cell. Biochem. 112: 3856-3862, 2011. (C) 2011 Wiley Periodicals, Inc.
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