title: USP7 regulates the stability and function of HLTF through deubiquitination.
abstract: 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.
authors.affiliation: Department of Respiratory Diseases, Minhang District Central Hospital, Shanghai, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Qing
authors.forename: Lu
authors.initials: L
authors.lastname: Han
authors.forename: Liu
authors.initials: L
authors.lastname: Bin
authors.forename: Lu
authors.initials: L
authors.lastname: Yan
authors.forename: Wen Xue
authors.initials: WX
authors.lastname: Ping
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000502:physiology*; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000502:physiology*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000502:physiology*; D000076084:Ubiquitin-Specific Peptidase 7; D054875:Ubiquitination
chemical_list: D004268:DNA-Binding Proteins; C100023:HLTF protein, human; D018809:Proliferating Cell Nuclear Antigen; D014157:Transcription Factors; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7