ArticleThe Journal of biological chemistry2014
Ubiquitin-specific protease 7 regulates nucleotide excision repair through deubiquitinating XPC protein and preventing XPC protein from undergoing ultraviolet light-induced and VCP/p97 protein-regulated proteolysis.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 86 citations in OpenAlex.
- VCP at the crossroads of UPS and autophagy in cancer.Genes & diseases · 2027Review
- Ubiquitin's code: UPS orchestrating DNA repair and genomic stability under genotoxic stress.Molecular and cellular biochemistry · 2026Review
- USP7 at the Crossroads of Ubiquitin Signaling, Cell Cycle, and Tumorigenesis.Molecules (Basel, Switzerland) · 2025Review
- USP7 promotes temozolomide resistance by stabilizing MGMT in glioblastoma.Cell death & disease · 2025Article
- BTG3-dependent VCP/p97 nuclear translocation is required for efficient repair of UV-induced DNA lesions.Nucleic acids research · 2025Article
- ATAD5 functions as a regulatory platform for Ub-PCNA deubiquitination.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Valosin-Containing Protein (VCP): A Review of Its Diverse Molecular Functions and Clinical Phenotypes.International journal of molecular sciences · 2024Review
- The AAA-ATPase Ter94 regulates wing size in Drosophila by suppressing the Hippo pathway.Communications biology · 2024Article
- DoUBLing up: ubiquitin and ubiquitin-like proteases in genome stability.The Biochemical journal · 2024Review
- An Overview of the Deubiquitinase USP53: A Promising Diagnostic Marker and Therapeutic Target.Current protein & peptide science · 2024Review
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Detection of oxaliplatin- and cisplatin-DNA lesions requires different global genome repair mechanisms that affect their clinical efficacy.NAR cancer · 2023Article
- RNAPII response to transcription-blocking DNA lesions in mammalian cells.The FEBS journal · 2023Review
- Systematic identification of factors involved in the silencing of germline genes in mouse embryonic stem cells.Nucleic acids research · 2023Article
- RNA interference screens discover proteases as synthetic lethal partners of PI3K inhibition in breast cancer cells.Theranostics · 2022Article
- Role of ubiquitin specific proteases in the immune microenvironment of prostate cancer: A new direction.Frontiers in oncology · 2022Review
- Nucleotide excision repair leaves a mark on chromatin: DNA damage detection in nucleosomes.Cellular and molecular life sciences : CMLS · 2021Review
- TIP60 governs the auto‑ubiquitination of UHRF1 through USP7 dissociation from the UHRF1/USP7 complex.International journal of oncology · 2021Article
- Ubiquitin-Specific Proteases: Players in Cancer Cellular Processes.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Timely upstream events regulating nucleotide excision repair by ubiquitin-proteasome system: ubiquitin guides the way.DNA repair · 2021Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Ubiquitin specific protease 7 (USP7) is a known deubiquitinating enzyme for tumor suppressor p53 and its downstream regulator, E3 ubiquitin ligase Mdm2. Here we report that USP7 regulates nucleotide excision repair (NER) via deubiquitinating xeroderma pigmentosum complementation group C (XPC) protein, a critical damage recognition factor that binds to helix-distorting DNA lesions and initiates NER. XPC is ubiquitinated during the early stage of NER of UV light-induced DNA lesions. We demonstrate that transiently compromising cellular USP7 by siRNA and chemical inhibition leads to accumulation of ubiquitinated forms of XPC, whereas complete USP7 deficiency leads to rapid ubiquitin-mediated XPC degradation upon UV irradiation. We show that USP7 physically interacts with XPC in vitro and in vivo. Overexpression of wild-type USP7, but not its catalytically inactive or interaction-defective mutants, reduces the ubiquitinated forms of XPC. Importantly, USP7 efficiently deubiquitinates XPC-ubiquitin conjugates in deubiquitination assays in vitro. We further show that valosin-containing protein (VCP)/p97 is involved in UV light-induced XPC degradation in USP7-deficient cells. VCP/p97 is readily recruited to DNA damage sites and colocalizes with XPC. Chemical inhibition of the activity of VCP/p97 ATPase causes an increase in ubiquitinated XPC on DNA-damaged chromatin. Moreover, USP7 deficiency severely impairs the repair of cyclobutane pyrimidine dimers and, to a lesser extent, affects the repair of 6-4 photoproducts. Taken together, our findings uncovered an important role of USP7 in regulating NER via deubiquitinating XPC and by preventing its VCP/p97-regulated proteolysis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.