ArticleOncogene2015
Homeodomain-interacting protein kinase 2 regulates DNA damage response through interacting with heterochromatin protein 1γ.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Clinicopathological and Prognostic Significance of CBX3 Expression in Human Cancer: a Systematic Review and Meta-analysis.Disease markers · 2020Pooled it
- CBX3 aggravates nucleus pulposus cell apoptosis and extracellular matrix degradation in vitro via repressing SESN2-mediated mitophagy in an H3K9me3-dependent manner.Molecular biology reports · 2026Article
- Lipid Conjugation of a Photoprotective Meadowfoam (Biomolecules · 2026Article
- Cbx3a/HP1γ Deficiency Disrupts Meiotic Progression and Triggers Germ Cell Apoptosis in Nile Tilapia.Biomolecules · 2026Article
- Molecular insights for the tumor suppressor role of SPOP in prostate cancer.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Challenges and opportunities for the diverse substrates of SPOP E3 ubiquitin ligase in cancer.Theranostics · 2025Review
- Lactate reprograms glioblastoma immunity through CBX3-regulated histone lactylation.The Journal of clinical investigation · 2024Article
- ERCC4: a potential regulatory factor in inflammatory bowel disease and inflammation-associated colorectal cancer.Frontiers in endocrinology · 2024Review
- Homeodomain-interacting protein kinase 2 regulates NLRP3 inflammasome activation through endoplasmic reticulum stress in septic liver injury.The Journal of international medical research · 2023Article
- CBX3 regulated by miR-139 promotes the development of HCC by regulating cell cycle progression.Cell cycle (Georgetown, Tex.) · 2022Article
- CBX3 accelerates the malignant progression of glioblastoma multiforme by stabilizing EGFR expression.Oncogene · 2022Article
- HP1 maintains protein stability of H3K9 methyltransferases and demethylases.EMBO reports · 2022Article
- Analysis of Pan-Cancer Revealed the Immunological and Prognostic Potential of CBX3 in Human Tumors.Frontiers in medicine · 2022Article
- MicroRNA-889-3p restrains the proliferation and epithelial-mesenchymal transformation of lung cancer cells via down-regulation of Homeodomain-interacting protein kinase 1.Bioengineered · 2021Article
- Prostate cancer-associated SPOP mutations lead to genomic instability through disruption of the SPOP-HIPK2 axis.Nucleic acids research · 2021Article
- A novel isoform of Homeodomain-interacting protein kinase-2 promotes YAP/TEAD transcriptional activity in NSCLC cells.Oncotarget · 2021Article
- A Functional Polymorphism in Accessible Chromatin Region Confers Risk of Non-Small Cell Lung Cancer in Chinese Population.Frontiers in oncology · 2021Article
- HIPK2 sustains inflammatory cytokine production by promoting endoplasmic reticulum stress in macrophages.Experimental and therapeutic medicine · 2020Article
- How HP1 Post-Translational Modifications Regulate Heterochromatin Formation and Maintenance.Cells · 2020Review
- CBX3 Promotes Gastric Cancer Progression and Affects Factors Related to Immunotherapeutic Responses.Cancer management and research · 2020Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Homeodomain-interacting protein kinase 2 (HIPK2) is a potential tumor suppressor that has a crucial role in the DNA damage response (DDR) by regulating cell-cycle checkpoint activation and apoptosis. However, it is unclear whether HIPK2 exerts distinct roles in DNA damage repair. The aim of this study was to identify novel target molecule(s) of HIPK2, which mediates HIPK2-dependent DNA damage repair. HIPK2-knockdown human colon cancer cells (HCT116) or hipk1/hipk2 double-deficient mouse embryonic fibroblasts could not remove histone H2A.X phosphorylated at Ser139 (γH2A.X) after irradiation with a sublethal dose (10 J/m(2)) of ultraviolet (UV)-C, resulting in apoptosis. Knockdown of HIPK2 in p53-null HCT116 cells similarly promoted the UV-C-induced γH2A.X accumulation and apoptosis. Proteomic analysis of HIPK2-associated proteins using liquid chromatography-tandem mass spectrometry identified heterochromatin protein 1γ (HP1γ) as a novel target for HIPK2. Immunoprecipitation experiments with HCT116 cells expressing FLAG-tagged HIPK2 and one of the HA-tagged HP1 family members demonstrated that HIPK2 specifically associated with HP1γ, but not with HP1α or HP1β, through its chromo-shadow domain. Mutation of the HP1box motif (883-PTVSV-887) within HIPK2 abolished the association. HP1γ knockdown also enhanced accumulation of γH2A.X and apoptosis after sublethal UV-C irradiation. In vitro kinase assay demonstrated an HP1γ-phosphorylating activity of HIPK2. Sublethal UV-C irradiation phosphorylated HP1γ. This phosphorylation was absent in endogenous HIPK2-silenced cells with HIPK2 3'UTR siRNA. Overexpression of FLAG-HIPK2, but not the HP1box-mutated or kinase-dead HIPK2 mutant, in the HIPK2-silenced cells increased HP1γ binding to trimethylated (Lys9) histone H3 (H3K9me3), rescued the UV-C-induced phosphorylation of HP1γ, triggered release of HP1γ from histone H3K9me3 and suppressed γH2A.X accumulation. Our results suggest that HIPK2-dependent phosphorylation of HP1γ may participate in the regulation of dynamic interaction between HP1γ and histone H3K9me3 to promote DNA damage repair. This HIPK2/HP1γ pathway may uncover a new functional aspect of HIPK2 as a tumor suppressor.
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