Premium
USP7 regulates the stability and function of HLTF through deubiquitination
Author(s) -
Qing Peng,
Han Lu,
Bin Liu,
Yan Lu,
Ping Wen Xue
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23317
Subject(s) - proliferating cell nuclear antigen , microbiology and biotechnology , ubiquitin , gene silencing , chemistry , dna damage , transcription factor , biology , dna , gene , biochemistry
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. © 2011 Wiley Periodicals, Inc.