ArticleOncogene2009
The human protein kinase HIPK2 phosphorylates and downregulates the methyl-binding transcription factor ZBTB4.
Article in Oncogene, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- HIPK1 Inhibition Protects against Pathological Cardiac Hypertrophy by Inhibiting the CREB-C/EBPβ Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Identification of ZBTB4 as an immunological biomarker that can inhibit the proliferation and invasion of pancreatic cancer.BMC cancer · 2023Article
- miRNA-576-5p promotes endometrial cancer cell growth and metastasis by targeting ZBTB4.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Review
- Regulation of the SIAH2-HIF-1 Axis by Protein Kinases and Its Implication in Cancer Therapy.Frontiers in cell and developmental biology · 2021Review
- Article
- Chromatin Targeting of HIPK2 Leads to Acetylation-Dependent Chromatin Decondensation.Frontiers in cell and developmental biology · 2020Article
- Expression of Zinc Finger and BTB Domain-Containing 4 in Colorectal Cancer and Its Clinical Significance.Cancer management and research · 2020Article
- Genetic screens reveal mechanisms for the transcriptional regulation of tissue-specific genes in normal cells and tumors.Nucleic acids research · 2019Article
- MicroRNA-106b promotes the proliferation, migration and invasion of retinoblastoma cells by inhibiting the expression of ZBTB4 protein.Experimental and therapeutic medicine · 2018Article
- Variants regulating ZBTB4 are associated with age-at-onset of Alzheimer's disease.Genes, brain, and behavior · 2018Article
- An RNA interference screen identifies druggable regulators of MeCP2 stability.Science translational medicine · 2017Article
- Homeodomain-Interacting Protein Kinase-2: A Critical Regulator of the DNA Damage Response and the Epigenome.International journal of molecular sciences · 2016Review
- Homeodomain-interacting protein kinase 2 regulates DNA damage response through interacting with heterochromatin protein 1γ.Oncogene · 2015Article
- MBD4 cooperates with DNMT1 to mediate methyl-DNA repression and protects mammalian cells from oxidative stress.Epigenetics · 2014Article
- Synthesis and properties of a selective inhibitor of homeodomain-interacting protein kinase 2 (HIPK2).PloS one · 2014Article
- Homeodomain-interacting protein kinase 2-dependent repression of myogenic differentiation is relieved by its caspase-mediated cleavage.Nucleic acids research · 2013Article
- Emerging role of DYRK family protein kinases as regulators of protein stability in cell cycle control.Cell cycle (Georgetown, Tex.) · 2012Review
- Article
- Homeodomain-interacting protein kinase-2 stabilizes p27(kip1) by its phosphorylation at serine 10 and contributes to cell motility.The Journal of biological chemistry · 2011Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HIPK2 is a eukaryotic Serine-Threonine kinase that controls cellular proliferation and survival in response to exogenous signals. Here, we show that the human transcription factor ZBTB4 is a new target of HIPK2. The two proteins interact in vitro, colocalize and associate in vivo, and HIPK2 phosphorylates several conserved residues of ZBTB4. Overexpressing HIPK2 causes the degradation of ZBTB4, whereas overexpressing a kinase-deficient mutant of HIPK2 has no effect. The chemical activation of HIPK2 also decreases the amount of ZBTB4 in cells. Conversely, the inhibition of HIPK2 by drugs or by RNA interference causes a large increase in ZBTB4 levels. This negative regulation of ZBTB4 by HIPK2 occurs under normal conditions of cell growth. In addition, the degradation is increased by DNA damage. These findings have two consequences. First, we have recently shown that ZBTB4 inhibits the transcription of p21. Therefore, the activation of p21 by HIPK2 is two-pronged: stimulation of the activator p53, and simultaneous repression of the inhibitor ZBTB4. Second, ZBTB4 is also known to bind methylated DNA and repress methylated sequences. Consequently, our findings raise the possibility that HIPK2 might influence the epigenetic regulation of gene expression at loci that remain to be identified.
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