ArticleThe Journal of biological chemistry2015
The Tyrosine Kinase c-Abl Promotes Homeodomain-interacting Protein Kinase 2 (HIPK2) Accumulation and Activation in Response to DNA Damage.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- The Abl1 tyrosine kinase is a key player in doxorubicin-induced cardiomyopathy and its p53/p73 cell death mediated signaling differs in atrial and ventricular cardiomyocytes.Journal of translational medicine · 2024Article
- SIAH1-mediated RPS3 ubiquitination contributes to chemosensitivity in epithelial ovarian cancer.Aging · 2022Article
- The c-Abl inhibitor, radotinib induces apoptosis in multiple myeloma cells via mitochondrial-dependent pathway.Scientific reports · 2021Article
- The hippo pathway provides novel insights into lung cancer and mesothelioma treatment.Journal of cancer research and clinical oncology · 2018Review
- Homeodomain-interacting protein kinase 2 (HIPK2): a promising target for anti-cancer therapies.Oncotarget · 2017Review
- EGFR induces DNA decomposition via phosphodiester bond cleavage.Scientific reports · 2017Article
- HIPK2-T566 autophosphorylation diversely contributes to UV- and doxorubicin-induced HIPK2 activation.Oncotarget · 2017Article
- Homeodomain-Interacting Protein Kinase-2: A Critical Regulator of the DNA Damage Response and the Epigenome.International journal of molecular sciences · 2016Review
- Changes in 30K protein synthesis during delayed degeneration of the silk gland by a caspase-dependent pathway in a Bombyx (silkworm) mutant.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2016Article
- The DNA damage-induced cell death response: a roadmap to kill cancer cells.Cellular and molecular life sciences : CMLS · 2016Review
- HIPK family kinases bind and regulate the function of the CCR4-NOT complex.Molecular biology of the cell · 2016Article
- Transcription Factors in the Cellular Response to Charged Particle Exposure.Frontiers in oncology · 2016Review
- Cross talk of tyrosine kinases with the DNA damage signaling pathways.Nucleic acids research · 2015Review
- Role of the nucleus in apoptosis: signaling and execution.Cellular and molecular life sciences : CMLS · 2015Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The non-receptor tyrosine kinase c-Abl is activated in response to DNA damage and induces p73-dependent apoptosis. Here, we investigated c-Abl regulation of the homeodomain-interacting protein kinase 2 (HIPK2), an important regulator of p53-dependent apoptosis. c-Abl phosphorylated HIPK2 at several sites, and phosphorylation by c-Abl protected HIPK2 from degradation mediated by the ubiquitin E3 ligase Siah-1. c-Abl and HIPK2 synergized in activating p53 on apoptotic promoters in a reporter assay, and c-Abl was required for endogenous HIPK2 accumulation and phosphorylation of p53 at Ser(46) in response to DNA damage by γ- and UV radiation. Accumulation of HIPK2 in nuclear speckles and association with promyelocytic leukemia protein (PML) in response to DNA damage were also dependent on c-Abl activity. At high cell density, the Hippo pathway inhibits DNA damage-induced c-Abl activation. Under this condition, DNA damage-induced HIPK2 accumulation, phosphorylation of p53 at Ser(46), and apoptosis were attenuated. These data demonstrate a new mechanism for the induction of DNA damage-induced apoptosis by c-Abl and illustrate network interactions between serine/threonine and tyrosine kinases that dictate cell fate.
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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.