ArticleCell cycle (Georgetown, Tex.)2014
Src kinase modulates the apoptotic p53 pathway by altering HIPK2 localization.
Article in Cell cycle (Georgetown, Tex.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Article
- WIP1 is a novel specific target for growth hormone action.iScience · 2023Article
- HIPK2 in the physiology of nervous system and its implications in neurological disorders.Biochimica et biophysica acta. Molecular cell research · 2023Review
- The Sweet Side of HIPK2.Cancers · 2023Review
- Early SRC activation skews cell fate from apoptosis to senescence.Science advances · 2022Article
- Sublethal doxorubicin promotes migration and invasion of breast cancer cells: role of Src Family non-receptor tyrosine kinases.Breast cancer research : BCR · 2021Article
- DAZAP2 acts as specifier of the p53 response to DNA damage.Nucleic acids research · 2021Article
- Inactivation of homeodomain-interacting protein kinase 2 promotes oral squamous cell carcinoma metastasis through inhibition of P53-dependent E-cadherin expression.Cancer science · 2021Article
- Phosphorylation of BCKDK of BCAA catabolism at Y246 by Src promotes metastasis of colorectal cancer.Oncogene · 2020Article
- Article
- Effects of Y361-auto-phosphorylation on structural plasticity of the HIPK2 kinase domain.Protein science : a publication of the Protein Society · 2018Article
- p300-mediated acetylation increased the protein stability of HIPK2 and enhanced its tumor suppressor function.Scientific reports · 2017Article
- Homeodomain-interacting protein kinase 2 (HIPK2): a promising target for anti-cancer therapies.Oncotarget · 2017Review
- HIPK2-T566 autophosphorylation diversely contributes to UV- and doxorubicin-induced HIPK2 activation.Oncotarget · 2017Article
- Hyperglycemia triggers HIPK2 protein degradation.Oncotarget · 2017Article
- The DNA damage-induced cell death response: a roadmap to kill cancer cells.Cellular and molecular life sciences : CMLS · 2016Review
- Role of miR-27a, miR-181a and miR-20b in gastric cancer hypoxia-induced chemoresistance.Cancer biology & therapy · 2016Article
- Crystal Structure of the CTP1L Endolysin Reveals How Its Activity Is Regulated by a Secondary Translation Product.The Journal of biological chemistry · 2016Article
- HIPK2 restricts SIRT1 activity upon severe DNA damage by a phosphorylation-controlled mechanism.Cell death and differentiation · 2016Article
- Dysregulation of ubiquitin ligases in cancer.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2015Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-receptor tyrosine kinase Src is a master regulator of cell proliferation. Hyperactive Src is a potent oncogene and a driver of cellular transformation and carcinogenesis. Homeodomain-interacting protein kinase 2 (HIPK2) is a tumor suppressor mediating growth suppression and apoptosis upon genotoxic stress through phosphorylation of p53 at Ser46. Here we show that Src phosphorylates HIPK2 and changes its subcellular localization. Using mass spectrometry we identified 9 Src-mediated Tyr-phosphorylation sites within HIPK2, 5 of them positioned in the kinase domain. By means of a phosphorylation-specific antibody we confirm that Src mediates phosphorylation of HIPK2 at Tyr354. We demonstrate that ectopic expression of Src increases the half-life of HIPK2 by interfering with Siah-1-mediated HIPK2 degradation. Moreover, we find that hyperactive Src binds HIPK2 and redistributes HIPK2 from the cell nucleus to the cytoplasm, where both kinases partially colocalize. Accordingly, we find that hyperactive Src decreases chemotherapeutic drug-induced p53 Ser46 phosphorylation and apoptosis activation. Together, our results suggest that Src kinase suppresses the apoptotic p53 pathway by phosphorylating HIPK2 and relocalizing the kinase to the cytoplasm.
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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.