ArticleThe EMBO journal2015
Noncanonical regulation of alkylation damage resistance by the OTUD4 deubiquitinase.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- Brain DNA methylomic analysis of frontotemporal lobar degeneration reveals OTUD4 in shared dysregulated signatures across pathological subtypes.Acta neuropathologica · 2023Pooled it
- OTUD4 stabilizes CYLD and counteracts BCL3 K63-linked polyubiquitination to suppress melanoma progression.Cell death & disease · 2026Article
- E3 ligase LMO7 promotes ALKBH2 ubiquitination to sensitize MGMT-deficient glioblastoma to temozolomide.Cell death & disease · 2026Article
- Mutant ribosomal protein RPS15 drives B cell malignancy through oxidative stress and genomic instability.Nature communications · 2026Article
- USP7 deubiquitinase stabilizes FAN1 to support DNA crosslink repair and suppress CAG repeat expansion.Nature communications · 2026Article
- OTU deubiquitinases in disease: roles and targeting.Trends in molecular medicine · 2026Review
- OTUD4 Inhibits Prostate Cancer by Deubiquitinating MYH9.Oncology research · 2026Article
- USP7 promotes temozolomide resistance by stabilizing MGMT in glioblastoma.Cell death & disease · 2025Article
- DNA repair and the contribution to chemotherapy resistance.Genome medicine · 2025Review
- Ubiquitin-dependent proteasomal degradation of small hepatitis B virus surface antigen mediated by TRIM21 and antagonized by OTUD4.Journal of virology · 2025Article
- Deubiquitinating Enzyme OTUDs: Focus on Cancers and Antiviral Response.Oncology research · 2025Review
- RNA binding proteins potentially regulate alternative splicing of immune-related genes during the progression of coronary artery disease.Experimental biology and medicine (Maywood, N.J.) · 2025Article
- OTU deubiquitinases in cancer pathogenesis and precision therapy.American journal of cancer research · 2025Review
- Erasing marks: Functions of plant deubiquitylating enzymes in modulating the ubiquitin code.The Plant cell · 2024Review
- The Roles of AGTRAP, ALKBH3, DIVERSIN, NEDD8 and RRM1 in Glioblastoma Pathophysiology and Prognosis.Biomedicines · 2024Article
- DoUBLing up: ubiquitin and ubiquitin-like proteases in genome stability.The Biochemical journal · 2024Review
- Pharmacological suppression of the OTUD4/CD73 proteolytic axis revives antitumor immunity against immune-suppressive breast cancers.The Journal of clinical investigation · 2024Article
- OTUD4 promotes the progression of glioblastoma by deubiquitinating CDK1 and activating MAPK signaling pathway.Cell death & disease · 2024Article
- Non-canonical regulation of the reactivation of an oncogenic herpesvirus by the OTUD4-USP7 deubiquitinases.PLoS pathogens · 2024Article
- In the moonlight: non-catalytic functions of ubiquitin and ubiquitin-like proteases.Frontiers in molecular biosciences · 2024Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Repair of DNA alkylation damage is critical for genomic stability and involves multiple conserved enzymatic pathways. Alkylation damage resistance, which is critical in cancer chemotherapy, depends on the overexpression of alkylation repair proteins. However, the mechanisms responsible for this upregulation are unknown. Here, we show that an OTU domain deubiquitinase, OTUD4, is a positive regulator of ALKBH2 and ALKBH3, two DNA demethylases critical for alkylation repair. Remarkably, we find that OTUD4 catalytic activity is completely dispensable for this function. Rather, OTUD4 is a scaffold for USP7 and USP9X, two deubiquitinases that act directly on the AlkB proteins. Moreover, we show that loss of OTUD4, USP7, or USP9X in tumor cells makes them significantly more sensitive to alkylating agents. Taken together, this work reveals a novel, noncanonical mechanism by which an OTU family deubiquitinase regulates its substrates, and provides multiple new targets for alkylation chemotherapy sensitization of tumors.
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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.