ArticleNucleic acids research2013
Homeodomain-interacting protein kinase 2-dependent repression of myogenic differentiation is relieved by its caspase-mediated cleavage.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Cardiomyocytes HIPK2 regulates myocardial inflammation and heart function through purinergic signaling.Cell communication and signaling : CCS · 2026Article
- Integrative Multi-omics Analysis of the Human Skeletal Muscle Response to Endurance or Resistance Exercise: Findings from the Molecular Transducers of Physical Activity Consortium (MoTrPAC).bioRxiv : the preprint server for biology · 2026Article
- Article
- HIPK2 C-terminal domain inhibits NF-κB signaling and renal inflammation in kidney injury.JCI insight · 2024Article
- Functions of SRPK, CLK and DYRK kinases in stem cells, development, and human developmental disorders.FEBS letters · 2023Review
- Phenotypic Effects of Homeodomain-Interacting Protein Kinase 2 Deletion in Mice.International journal of molecular sciences · 2021Article
- Small-molecule probe reveals a kinase cascade that links stress signaling to TCF/LEF and Wnt responsiveness.Cell chemical biology · 2021Article
- Article
- PTRH2: an adhesion regulated molecular switch at the nexus of life, death, and differentiation.Cell death discovery · 2020Review
- An Alternative Splice Variant of HIPK2 with Intron Retention Contributes to Cytokinesis.Cells · 2020Article
- Chromatin Targeting of HIPK2 Leads to Acetylation-Dependent Chromatin Decondensation.Frontiers in cell and developmental biology · 2020Article
- Homeodomain-interacting protein kinase 2 suppresses proliferation and aerobic glycolysis via ERK/cMyc axis in pancreatic cancer.Cell proliferation · 2019Article
- Article
- Arsenic-Induced Activation of the Homeodomain-Interacting Protein Kinase 2 (HIPK2) to cAMP-Response Element Binding Protein (CREB) Axis.Journal of molecular biology · 2017Article
- Homeodomain-Interacting Protein Kinase-2: A Critical Regulator of the DNA Damage Response and the Epigenome.International journal of molecular sciences · 2016Review
- HIPK family kinases bind and regulate the function of the CCR4-NOT complex.Molecular biology of the cell · 2016Article
- The beneficial role of proteolysis in skeletal muscle growth and stress adaptation.Skeletal muscle · 2016Review
- HDAC4 as a potential therapeutic target in neurodegenerative diseases: a summary of recent achievements.Frontiers in cellular neuroscience · 2015Review
- Global MEF2 target gene analysis in cardiac and skeletal muscle reveals novel regulation of DUSP6 by p38MAPK-MEF2 signaling.Nucleic acids research · 2014Article
- HIPK2 modification code for cell death and survival.Molecular & cellular oncologyReview
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Differentiation of skeletal muscle cells is accompanied by drastic changes in gene expression programs that depend on activation and repression of genes at defined time points. Here we identify the serine/threonine kinase homeodomain-interacting protein kinase 2 (HIPK2) as a corepressor that inhibits myocyte enhancer factor 2 (MEF2)-dependent gene expression in undifferentiated myoblasts. Downregulation of HIPK2 expression by shRNAs results in elevated expression of muscle-specific genes, whereas overexpression of the kinase dampens transcription of these genes. HIPK2 is constitutively associated with a multi-protein complex containing histone deacetylase (HDAC)3 and HDAC4 that serves to silence MEF2C-dependent transcription in undifferentiated myoblasts. HIPK2 interferes with gene expression on phosphorylation and HDAC3-dependent deacetylation of MEF2C. Ongoing muscle differentiation is accompanied by elevated caspase activity, which results in caspase-mediated cleavage of HIPK2 following aspartic acids 916 and 977 and the generation of a C-terminally truncated HIPK2 protein. The short form of the kinase loses its affinity to the repressive multi-protein complex and its ability to bind HDAC3 and HDAC4, thus alleviating its repressive function for expression of muscle genes. This study identifies HIPK2 as a further protein that determines the threshold and kinetics of gene expression in proliferating myoblasts and during the initial steps of myogenesis.
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