ArticleThe Journal of biological chemistry2010
Pyk2 inhibition of p53 as an adaptive and intrinsic mechanism facilitating cell proliferation and survival.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 78 citations in OpenAlex.
- Loss of endothelial cell FAK represses cisplatin-induced vascular senescence in distal niches to reduce lung metastatic burden.Research square · 2026Article
- Glutamate-induced nuclear translocation of PYK2 in hippocampal neurons, interaction with MBD2, and role in cell death in a model of epilepsy.Cell death & disease · 2026Article
- JAK2/STAT3-dependent regulation of MDM4/MDM2-p53 signaling in methotrexate-induced ferroptosis and nephrotoxicity.Archives of pharmacal research · 2026Article
- Tumor-associated mesenchymal stem/stromal cells in tumor microenvironment and carcinogenesis.Experimental hematology & oncology · 2025Review
- Inducible FAK loss but not FAK inhibition in endothelial cells of PYK2-null mice activates p53 tumor suppressor to prevent tumor growth.Molecular biology of the cell · 2025Article
- Research progress of PYK2 in digestive system diseases.Frontiers in immunology · 2025Review
- Focal adhesion kinase signaling - tumor vulnerabilities and clinical opportunities.Journal of cell science · 2024Review
- Targeting FAK/PYK2 with SJP1602 for Anti-Tumor Activity in Triple-Negative Breast Cancer.Current issues in molecular biology · 2023Article
- Pyk2 regulates sepsis-induced lung injury via ferroptosis.Iranian journal of basic medical sciences · 2023Article
- Activated PyK2 and Its Associated Molecules Transduce Cellular Signaling from the Cancerous Milieu for Cancer Metastasis.International journal of molecular sciences · 2022Review
- New Insights on the Nuclear Functions and Targeting of FAK in Cancer.International journal of molecular sciences · 2022Review
- Systematic Identification of Genomic Markers for Guiding Iron Oxide Nanoparticles in Cervical Cancer Based on Translational Bioinformatics.International journal of nanomedicine · 2022Article
- FAK inhibitors as promising anticancer targets: present and future directions.Future medicinal chemistry · 2021Review
- The Non-receptor Tyrosine Kinase Pyk2 in Brain Function and Neurological and Psychiatric Diseases.Frontiers in synaptic neuroscience · 2021Review
- FAK Family Kinases in Vascular Diseases.International journal of molecular sciences · 2020Review
- Metformin prevention of doxorubicin resistance in MCF-7 and MDA-MB-231 involves oxidative stress generation and modulation of cell adaptation genes.Scientific reports · 2019Article
- Role of Pyk2 in Human Cancers.Medical science monitor : international medical journal of experimental and clinical research · 2018Review
- Endogenous Control Mechanisms of FAK and PYK2 and Their Relevance to Cancer Development.Cancers · 2018Review
- Review
- Key Players of Cisplatin Resistance: Towards a Systems Pharmacology Approach.International journal of molecular sciences · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Pyk2 is a cytoplasmic tyrosine kinase related to focal adhesion kinase (FAK). Compensatory Pyk2 expression occurs upon FAK loss in mice. However, the impact of Pyk2 up-regulation remains unclear. Previous studies showed that nuclear-localized FAK promotes cell proliferation and survival through FAK FERM domain-enhanced p53 tumor suppressor degradation (Lim, S. T., Chen, X. L., Lim, Y., Hanson, D. A., Vo, T. T., Howerton, K., Larocque, N., Fisher, S. J., Schlaepfer, D. D., and Ilic, D. (2008) Mol. Cell 29, 9-22). Here, we show that FAK knockdown triggered p53 activation and G(1) cell cycle arrest in human umbilical vein endothelial cells after 4 days. However, by 7 days elevated Pyk2 expression occurred with a reduction in p53 levels and the release of the G(1) block under conditions of continued FAK knockdown. To determine whether Pyk2 regulates p53, experiments were performed in FAK(-/-)p21(-/-) mouse embryo fibroblasts expressing endogenous Pyk2 and in ID8 ovarian carcinoma cells expressing both Pyk2 and FAK. In both cell lines, Pyk2 knockdown increased p53 levels and inhibited cell proliferation associated with G(1) cell cycle arrest. Pyk2 FERM domain re-expression was sufficient to reduce p53 levels and promote increased BrdUrd incorporation. Pyk2 FERM promoted Mdm2-dependent p53 ubiquitination. Pyk2 FERM effects on p53 were blocked by proteasomal inhibition or mutational-inactivation of Pyk2 FERM nuclear localization. Staurosporine stress of ID8 cells promoted endogenous Pyk2 nuclear accumulation and enhanced Pyk2 binding to p53. Pyk2 knockdown potentiated ID8 cell death upon staurosporine addition. Moreover, Pyk2 FERM expression in human fibroblasts upon FAK knockdown prevented cisplatin-mediated apoptosis. Our studies demonstrate that nuclear Pyk2 functions to limit p53 levels, thus facilitating cell growth and survival in a kinase-independent manner.
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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.