ArticleCell cycle (Georgetown, Tex.)2014
USP3 counteracts RNF168 via deubiquitinating H2A and γH2AX at lysine 13 and 15.
Article in Cell cycle (Georgetown, Tex.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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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.
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Who cites it
70 citing papers in PubMed, 110 citations in OpenAlex.
- Unique gluing effect of ASXL1 K351 monoubiquitination stimulates the PR-DUB activity.Nature chemical biology · 2026Article
- ZnF-UBP domains regulate deubiquitinase activity by relieving ubiquitin product inhibition.Nature communications · 2026Article
- Ubiquitin's code: UPS orchestrating DNA repair and genomic stability under genotoxic stress.Molecular and cellular biochemistry · 2026Review
- Chromatin Remodeling, DNA Double-Strand Break Repair, and Human Disease: How a Breakup Changes You.Biomolecules · 2026Review
- Histone Phosphorylation in DNA Damage Response.International journal of molecular sciences · 2025Review
- Review
- USP14 inhibition promotes DNA damage repair and represses ovarian granulosa cell senescence in premature ovarian insufficiency.Journal of translational medicine · 2024Article
- USP3: Key deubiquitylation enzyme in human diseases.Cancer science · 2024Review
- Ubiquitin specific peptidase 3: an emerging deubiquitinase that regulates physiology and diseases.Cell death discovery · 2024Review
- DoUBLing up: ubiquitin and ubiquitin-like proteases in genome stability.The Biochemical journal · 2024Review
- USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway.Cell death & disease · 2024Article
- Article
- USP3 plays a critical role in the induction of innate immune tolerance.EMBO reports · 2023Article
- Ubiquitin E3 ligases in cancer: somatic mutation and amplification.BMB reports · 2023Review
- Protein degradation: expanding the toolbox to restrain cancer drug resistance.Journal of hematology & oncology · 2023Review
- Generation of site-specific ubiquitinated histones through chemical ligation to probe the specificities of histone deubiquitinases.Frontiers in epigenetics and epigenomics · 2023Article
- DNA Damage Response Regulation by Histone Ubiquitination.International journal of molecular sciences · 2022Review
- New answers to the old RIDDLE: RNF168 and the DNA damage response pathway.The FEBS journal · 2022Review
- Chromatin Ubiquitination Guides DNA Double Strand Break Signaling and Repair.Frontiers in cell and developmental biology · 2022Review
- The Chromatin Landscape Channels DNA Double-Strand Breaks to Distinct Repair Pathways.Frontiers in cell and developmental biology · 2022Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Histone ubiquitination plays a vital role in DNA damage response (DDR), which is important for maintaining genomic integrity in eukaryotic cells. In DDR, ubiquitination of histone H2A and γH2AX by the concerted action of ubiquitin (Ub) ligases, RNF168 and RNF8, generates a cascade of ubiquitination signaling. However, little is known about deubiquitinating enzymes (DUBs) that may catalyze the removal of Ub from these histones. This study demonstrated that USP3, an apparent DUB for mono-ubiquitinated H2A, is indeed the enzyme for deubiquitinating Ub conjugates of γH2AX and H2A from lysine sites, where the ubiquitination is initiated by RNF168. Here, we showed that ectopic expression of USP3 led to the deubiquitination of both H2A and γH2AX in response to UV-induced DNA damage. Moreover, ectopic USP3 expression abrogated FK2 antibody-reactive Ub-conjugate foci, which co-localize with damage-induced γH2AX foci. In addition, USP3 overexpression impaired the accumulation of downstream repair factors BRCA1 and 53BP1 at the damage sites in response to both UV and γ-irradiation. We further identified that the USP3 removes Ub at lysine 13 and 15 of H2A and γH2AX, as well as lysine 118 and 119 of H2AX in response to DNA damage. Taken together, the results suggested that USP3 is a negative regulator of ubiquitination signaling, counteracting RNF168- and RNF8-mediated ubiquitination.
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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.