ArticleMolecular cell2012
ATM-dependent downregulation of USP7/HAUSP by PPM1G activates p53 response to DNA damage.
Article in Molecular cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 142 citations in OpenAlex.
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- Targeting casein kinase 2 and ubiquitin-specific protease 7 to modulate RUNX2-mediated osteogenesis in chronic kidney disease.Molecular medicine (Cambridge, Mass.) · 2025Article
- A novel nuclear RNA HSD52 scaffolding NONO/SFPQ complex modulates DNA damage repair to facilitate temozolomide resistance.Neuro-oncology · 2025Article
- Research progress of deubiquitinating enzymes in cerebral ischemia-reperfusion injury.Frontiers in aging neuroscience · 2025Review
- PPM1G and its diagnostic, prognostic and therapeutic potential in HCC (Review).International journal of oncology · 2024Review
- Forward genetic approach identifies a phylogenetically conserved serine residue critical for the catalytic activity of UBIQUITIN-SPECIFIC PROTEASE 12 in Arabidopsis.Scientific reports · 2024Article
- Targeting CK2 eliminates senescent cells and prolongs lifespan in Zmpste24-deficient mice.Cell death & disease · 2024Article
- PPM1G promotes cell proliferation via modulating mutant GOF p53 protein expression in hepatocellular carcinoma.iScience · 2024Article
- Systematic identification of factors involved in the silencing of germline genes in mouse embryonic stem cells.Nucleic acids research · 2023Article
- Angiotensin-converting enzyme inhibitor promotes angiogenesis through Sp1/Sp3-mediated inhibition of notch signaling in male mice.Nature communications · 2023Article
- CK2 and the Hallmarks of Cancer.Biomedicines · 2022Review
- Article
- USP13 modulates the stability of the APC/C adaptor CDH1.Molecular biology reports · 2022Article
- Usp5, Usp34, and Otu1 deubiquitylases mediate DNA repair in Drosophila melanogaster.Scientific reports · 2022Article
- High expression of PPM1G is associated with the progression and poor prognosis of hepatocellular carcinoma.Cancer biomarkers : section A of Disease markers · 2022Article
- Administration of USP7 inhibitor P22077 inhibited cardiac hypertrophy and remodeling in Ang II-induced hypertensive mice.Frontiers in pharmacology · 2022Article
- The ORF45 Protein of Kaposi Sarcoma-Associated Herpesvirus Is an Inhibitor of p53 Signaling during Viral Reactivation.Journal of virology · 2021Article
- USP39 promotes non-homologous end-joining repair by poly(ADP-ribose)-induced liquid demixing.Nucleic acids research · 2021Article
36 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The deubiquitylation enzyme USP7/HAUSP plays a major role in regulating genome stability and cancer prevention by controlling the key proteins involved in the DNA damage response. Despite this important role in controlling other proteins, USP7 itself has not been recognized as a target for regulation. Here, we report that USP7 regulation plays a central role in DNA damage signal transmission. We find that stabilization of Mdm2, and correspondingly p53 downregulation in unstressed cells, is accomplished by a specific isoform of USP7 (USP7S), which is phosphorylated at serine 18 by the protein kinase CK2. Phosphorylation stabilizes USP7S and thus contributes to Mdm2 stabilization and downregulation of p53. After ionizing radiation, dephosphorylation of USP7S by the ATM-dependent protein phosphatase PPM1G leads to USP7S downregulation, followed by Mdm2 downregulation and accumulation of p53. Our findings provide a quantitative transmission mechanism of the DNA damage signal to coordinate a p53-dependent DNA damage response.
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