ArticleCell death and differentiation2013
The E3 ligase PIRH2 polyubiquitylates CHK2 and regulates its turnover.
Article in Cell death and differentiation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 47 citations in OpenAlex.
- FBXW7-mediated CHK2 regulation modulates DNA damage response and cellular stability in Huntington's disease.Cell death discovery · 2025Article
- USP39 at the crossroads of cancer immunity: regulating immune evasion and immunotherapy response through RNA splicing and ubiquitin signaling.Frontiers in immunology · 2025Review
- A missense variant effect map for the human tumor-suppressor protein CHK2.American journal of human genetics · 2024Article
- Tumour-intrinsic PDL1 signals regulate the Chk2 DNA damage response in cancer cells and mediate resistance to Chk1 inhibitors.Molecular cancer · 2024Article
- Pirh2 modulates the mitochondrial function and cytochrome c-mediated neuronal death during Alzheimer's disease.Cell death & disease · 2024Article
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- Article
- Inhibition of Pard3 promotes breast cancer metastasis via the USP28 mediated deubiquitination of Snail1.Heliyon · 2023Article
- Impaired end joining induces cardiac atrophy in a Hutchinson-Gilford progeria mouse model.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- SARS-CoV-2 and the DNA damage response.The Journal of general virology · 2023Review
- The Role of E3 Ligase Pirh2 in Disease.Cells · 2022Review
- Article
- Review
- Proteasomal Degradation of Zn-Dependent Hdacs: The E3-Ligases Implicated and the Designed Protacs That Enable Degradation.Molecules (Basel, Switzerland) · 2021Review
- The RNA-binding protein HuR is a novel target of Pirh2 E3 ubiquitin ligase.Cell death & disease · 2021Article
- Review
- Regulating tumor suppressor genes: post-translational modifications.Signal transduction and targeted therapy · 2020Review
- Coupling Conjugation and Deconjugation Activities to Achieve Cellular Ubiquitin Dynamics.Trends in biochemical sciences · 2020Review
- SIRT1 modulates cell cycle progression by regulating CHK2 acetylation-phosphorylation.Cell death and differentiation · 2020Article
- Writing and erasing MYC ubiquitination and SUMOylation.Genes & diseases · 2019Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
The serine threonine kinase checkpoint kinase 2 (CHK2) is a DNA damage checkpoint protein important for the ATM-p53 signaling pathway. In addition to its phosphorylation, CHK2 is also ubiquitylated, and both post-translational modifications are important for its function. However, although the mechanisms that regulate CHK2 phosphorylation are well established, those that control its ubiquitylation are not fully understood. In this study, we demonstrate that the ubiquitin E3 ligase PIRH2 (p53-induced protein with a RING (Really Interesting New Gene)-H2 domain) interacts with CHK2 and mediates its polyubiquitylation and proteasomal degradation. We show that the deubiquitylating enzyme USP28 forms a complex with PIRH2 and CHK2 and antagonizes PIRH2-mediated polyubiquitylation and proteasomal degradation of CHK2. We also provide evidence that CHK2 ubiquitylation by PIRH2 is dependent on its phosphorylation status. Cells deficient in Pirh2 displayed accumulation of Chk2 and enhanced hyperactivation of G1/S and G2/M cell-cycle checkpoints. This hyperactivation was, however, no longer observed in Pirh2-/-Chk2-/- cells, providing evidence for the importance of Chk2 regulation by Pirh2. These findings indicate that PIRH2 has central roles in the ubiquitylation of Chk2 and its turnover and in the regulation of its function.
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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.