ArticleThe Journal of experimental medicine2014
Tight regulation of ubiquitin-mediated DNA damage response by USP3 preserves the functional integrity of hematopoietic stem cells.
Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 80 citations in OpenAlex.
- USP3 stabilizes MIC19 by deubiquitination under hypoxic stress and promotes the progression of non-small cell lung cancer.Acta pharmacologica Sinica · 2026Article
- Usp7 Regulates Glial Lineage Cell-Specific Transcription Factors by Modulating Histone H2B Monoubiquitination.International journal of stem cells · 2024Article
- USP3 promotes DNA damage response and chemotherapy resistance through stabilizing and deubiquitinating SMARCA5 in prostate cancer.Cell death & disease · 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
- MYSM1 attenuates DNA damage signals triggered by physiologic and genotoxic DNA breaks.The Journal of allergy and clinical immunology · 2024Article
- USP3 inhibition is Active Against Chemo-resistant Hepatocellular Carcinoma Anchorage-independent GrowthCurrent molecular medicine · 2024Article
- USP3 plays a critical role in the induction of innate immune tolerance.EMBO reports · 2023Article
- ELF5 drives angiogenesis suppression though stabilizing WDTC1 in renal cell carcinoma.Molecular cancer · 2023Article
- SRSF1 is essential for primary follicle development by regulating granulosa cell survival via mRNA alternative splicing.Cellular and molecular life sciences : CMLS · 2023Article
- Generation of site-specific ubiquitinated histones through chemical ligation to probe the specificities of histone deubiquitinases.Frontiers in epigenetics and epigenomics · 2023Article
- Ubiquitin-specific protease 3 facilitates cell proliferation by deubiquitinating pyruvate kinase L/R in gallbladder cancer.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- DNA Damage Response Regulation by Histone Ubiquitination.International journal of molecular sciences · 2022Review
- Possible association of 16p11.2 copy number variation with altered lymphocyte and neutrophil counts.NPJ genomic medicine · 2022Article
- 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
- XRCC1 protects transcription from toxic PARP1 activity during DNA base excision repair.Nature cell biology · 2021Article
- Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma.BMC cancer · 2021Article
- Review
- Non-canonical function of DGCR8 in DNA double-strand break repair signaling and tumor radioresistance.Nature communications · 2021Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histone ubiquitination at DNA breaks is required for activation of the DNA damage response (DDR) and DNA repair. How the dynamic removal of this modification by deubiquitinating enzymes (DUBs) impacts genome maintenance in vivo is largely unknown. To address this question, we generated mice deficient for Ub-specific protease 3 (USP3; Usp3Δ/Δ), a histone H2A DUB which negatively regulates ubiquitin-dependent DDR signaling. Notably, USP3 deletion increased the levels of histone ubiquitination in adult tissues, reduced the hematopoietic stem cell (HSC) reserves over time, and shortened animal life span. Mechanistically, our data show that USP3 is important in HSC homeostasis, preserving HSC self-renewal, and repopulation potential in vivo and proliferation in vitro. A defective DDR and unresolved spontaneous DNA damage contribute to cell cycle restriction of Usp3Δ/Δ HSCs. Beyond the hematopoietic system, Usp3Δ/Δ animals spontaneously developed tumors, and primary Usp3Δ/Δ cells failed to preserve chromosomal integrity. These findings broadly support the regulation of chromatin ubiquitination as a key pathway in preserving tissue function through modulation of the response to genotoxic stress.
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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.