ArticleThe Journal of biological chemistry2012
Roles of Kruppel-associated Box (KRAB)-associated Co-repressor KAP1 Ser-473 Phosphorylation in DNA Damage Response.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- ENIGMA CHEK2gether Project: A Comprehensive Study Identifies Functionally Impaired CHEK2 Germline Missense Variants Associated with Increased Breast Cancer Risk.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Pooled it
- A Phase II Study of Berzosertib in Combination with Carboplatin Compared with Docetaxel with Carboplatin in Metastatic Castration-Resistant Prostate Cancer.Cancer research communications · 2026Trial
- MND1 protein mediates DNA damage repair and is a promising novel therapeutic target in hepatocellular carcinoma.Liver research (Beijing, China) · 2026Article
- ZNF184 negatively regulates HR repair and predicts poor prognosis in acute lymphoblastic leukemia.Nucleic acids research · 2026Article
- TIF1 Family Proteins as Modulators of Cell Death: Mechanisms and Therapeutic Opportunities.Biomolecules · 2026Review
- Roles of TIF1β in Leukemic Stem Cell Through SETDB1-Dependent and Independent Mechanisms.Cancer science · 2026Review
- The adeno-associated virus Rep proteins target PP4:SMEK1 by preventing substrate recruitment.PLoS pathogens · 2026Article
- SRSF3-TRIM28-MDC1 prevents DNA damage caused by R-loops in fatty liver disease in mice.JCI insight · 2026Article
- Identification of a lipid oxygen radical defense pathway and its epigenetic control.Nature communications · 2025Article
- HMMR has oncoprotein-like properties in neuroblastoma cells and high HMMR expression has independent prognostic potential in neuroblastomas.Scientific reports · 2025Article
- RSK1-driven TRIM28/E2F1 feedback loop promotes castration-resistant prostate cancer progression.The Journal of clinical investigation · 2025Article
- TRIM28-dependent developmental heterogeneity determines cancer susceptibility through distinct epigenetic states.Nature cancer · 2025Article
- KAP1 in antiviral immunity: dual roles in viral silencing and immune regulation.Frontiers in cellular and infection microbiology · 2025Review
- Multifaceted role ofMedComm · 2024Review
- Review
- TRIM28 in cancer and cancer therapy.Frontiers in genetics · 2024Review
- The epigenetic modifier HDAC2 and the checkpoint kinase ATM determine the responses of microsatellite instable colorectal cancer cells to 5-fluorouracil.Cell biology and toxicology · 2023Article
- Proteomics Reveals How the Tardigrade Damage Suppressor Protein Teaches Transfected Human Cells to Survive UV-C Stress.International journal of molecular sciences · 2023Article
- Acetylation-Mimic Mutation of TRIM28-Lys304 to Gln Attenuates the Interaction with KRAB-Zinc-Finger Proteins and Affects Gene Expression in Leukemic K562 Cells.International journal of molecular sciences · 2023Article
- Trim28 citrullination maintains mouse embryonic stem cell pluripotency via regulating Nanog and Klf4 transcription.Science China. Life sciences · 2023Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Kruppel-associated box (KRAB)-associated co-repressor KAP1 is an essential nuclear co-repressor for the KRAB zinc finger protein superfamily of transcriptional factors. Ataxia telangiectasia mutated (ATM)-Chk2 and ATM- and Rad3-related (ATR)-Chk1 are two primary kinase signaling cascades activated in response to DNA damage. A growing body of evidence suggests that ATM and ATR phosphorylate KAP1 at Ser-824 in response to DNA damage and regulate KAP1-dependent chromatin condensation, DNA repair, and gene expression. Here, we show that, depending on the type of DNA damage that occurs, KAP1 Ser-473 can be phosphorylated by ATM-Chk2 or ATR-Chk1 kinases. Phosphorylation of KAP1 at Ser-473 attenuated its binding to the heterochromatin protein 1 family proteins and inhibited its transcriptional repression of KRAB-zinc finger protein (KRAB-ZFP) target genes. Moreover, KAP1 Ser-473 phosphorylation induced by DNA damage stimulated KAP1-E2F1 binding. Overexpression of heterochromatin protein 1 significantly inhibited E2F1-KAP1 binding. Elimination of KAP1 Ser-473 phosphorylation increased E2F1-targeted proapoptotic gene expression and E2F1-induced apoptosis in response to DNA damage. Furthermore, loss of phosphorylation of KAP1 Ser-473 led to less BRCA1 focus formation and slower kinetics of loss of γH2AX foci after DNA damage. KAP1 Ser-473 phosphorylation was required for efficient DNA repair and cell survival in response to DNA damage. Our studies reveal novel functions of KAP1 Ser-473 phosphorylation under stress.
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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.