title: [Involvement of MAP-kinase cascades into the regulation of sodium butyrate induced premature cell senescence].
abstract: We studied the role of p38 kinase and JNK1,2 in the activation of the complex mTORC1 and the program of senescence induced by histone deacetylase inhibitor, sodium butyrate (NaBut), in mouse embryonic fibroblasts transformed by E1A+cHa-Ras oncogenes. It was found that transformants from knockouts for the genes p38, were able to implement the program of NaBut-induced senescence, according to the data of the cell cycle arrest, inhibition of proliferation, hypertrophic changes associated with the activation of mTORC1 and SA-beta-galactosidase activity. According to the behavior of these markers, cell knockouts for the genes jnk1,2 were unable to implement NaBut-induced senescence. Induction of senescence closely correlates with the activation of the complex mTORC1, as it was shown by inhibiting mTORC1 with rapamycin. We believe that JNK 1,2 kinases are required for mTORC1 activation and acquiring the markers of premature senescence, induced by NaBut in the E1A+cHa-Ras transformants.
authors: E Iu
authors: EIu
authors: Kochetkova
authors: T V
authors: TV
authors: Bykova
authors: S G
authors: SG
authors: Zubova
authors: T V
authors: TV
authors: Pospelova
mesh_terms: D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics; D005347:Fibroblasts; D056572:Histone Deacetylase Inhibitors; D020935:MAP Kinase Signaling System / Q000235:genetics; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism; D010766:Phosphorylation; D012964:Sodium / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D002087:Butyrates; D056572:Histone Deacetylase Inhibitors; D046912:Multiprotein Complexes; D012964:Sodium; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases