ArticleThe Journal of biological chemistry2015
p53 protein-mediated up-regulation of MAP kinase phosphatase 3 (MKP-3) contributes to the establishment of the cellular senescent phenotype through dephosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2).
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 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- ARL13B is regulated by the ERK/P90 pathway and mediates TMZ resistance in glioblastoma via microvesicles.Scientific reports · 2026Article
- Effects of Chlorogenic Acid on Cellular Senescence in an In Vitro Model of 3T3-L1 Murine Adipocytes.Molecules (Basel, Switzerland) · 2026Article
- A signaling pathway map of plasminogen activator inhibitor-1 (PAI-1/SERPINE-1): a review of an innovative frontier in molecular aging and cellular senescence.Cell communication and signaling : CCS · 2024Review
- Nuclear envelope budding inhibition slows down progerin-induced aging process.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The syntaxin-binding protein STXBP5 regulates progerin expression.Scientific reports · 2024Article
- Review
- Aging and obesity prime the methylome and transcriptome of adipose stem cells for disease and dysfunction.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- BMAL1/p53 mediating bronchial epithelial cell autophagy contributes to PM2.5-aggravated asthma.Cell communication and signaling : CCS · 2023Article
- Article
- ACTH(6-9)PGP Peptide Protects SH-SY5Y Cells from HMolecules (Basel, Switzerland) · 2021Article
- Methylsulfonylmethane inhibits cortisol-induced stress through p53-mediatedExperimental and therapeutic medicine · 2020Article
- Novel clinicopathological and molecular characterization of metanephric adenoma: a study of 28 cases.Diagnostic pathology · 2018Article
- Epithelial cell senescence: an adaptive response to pre-carcinogenic stresses?Cellular and molecular life sciences : CMLS · 2017Review
- Chinese 1 strain of Toxoplasma gondii excreted-secreted antigens negatively modulate Foxp3 via inhibition of the TGFßRII/Smad2/Smad3/Smad4 pathway.Journal of cellular and molecular medicine · 2017Article
- Systematic screening of isogenic cancer cells identifies DUSP6 as context-specific synthetic lethal target in melanoma.Oncotarget · 2017Article
- Activation of ERK1/2 Causes Pazopanib Resistance via Downregulation of DUSP6 in Synovial Sarcoma Cells.Scientific reports · 2017Article
- MicroRNAs in the thyroid.Best practice & research. Clinical endocrinology & metabolism · 2016Review
- Identification and characterization of the intercellular adhesion molecule-2 gene as a novel p53 target.Oncotarget · 2016Article
- Soluble egg antigens of Schistosoma japonicum induce senescence in activated hepatic stellate cells by activation of the STAT3/p53/p21 pathway.Scientific reports · 2016Article
- Article
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Growth arrest is one of the essential features of cellular senescence. At present, the precise mechanisms responsible for the establishment of the senescence-associated arrested phenotype are still incompletely understood. Given that ERK1/2 is one of the major kinases controlling cell growth and proliferation, we examined the possible implication of ERK1/2. Exposure of normal rat epithelial cells to etoposide caused cellular senescence, as manifested by enlarged cell size, a flattened cell body, reduced cell proliferation, enhanced β-galactosidase activity, and elevated p53 and p21. Senescent cells displayed a blunted response to growth factor-induced cell proliferation, which was preceded by impaired ERK1/2 activation. Further analysis revealed that senescent cells expressed a significantly higher level of mitogen-activated protein phosphatase 3 (MKP-3, a cytosolic ERK1/2-targeted phosphatase), which was suppressed by blocking the transcriptional activity of the tumor suppressor p53 with pifithrin-α. Inhibition of MKP-3 activity with a specific inhibitor or siRNA enhanced basal ERK1/2 phosphorylation and promoted cell proliferation. Apart from its role in growth arrest, impairment of ERK1/2 also contributed to the resistance of senescent cells to oxidant-elicited cell injury. These results therefore indicate that p53-mediated up-regulation of MKP-3 contributes to the establishment of the senescent cellular phenotype through dephosphorylating ERK1/2. Impairment of ERK1/2 activation could be an important mechanism by which p53 controls cellular senescence.
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