title: S6K in geroconversion.
abstract: Markers of cellular senescence depend in part on the MTOR (mechanistic target of rapamycin) pathway. MTOR participates in geroconversion, a conversion from reversible cell cycle arrest to irreversible senescence. Recently we demonstrated that hyper-induction of cyclin D1 during geroconversion was mostly dependent on MEK, whereas rapamycin only partially inhibited cyclin D1 accumulation. Here we show that, while not affecting cyclin D1, siRNA for p70S6K partially prevented loss of RP (replicative/regenerative potential) during p21-induced cell cycle arrest. Similarly, an inhibitor of p70 S6 kinase (PF-4708671) partially inhibited phosphorylation of S6 and preserved RP, while only marginally prevented cyclin D1 induction. Thus S6K and MEK play different roles in geroconversion.
authors.affiliation: Department of Cell Stress Biology; Roswell Park Cancer Institute; Buffalo, NY USA.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Leontieva
authors.forename: Zoya N
authors.initials: ZN
authors.lastname: Demidenko
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Blagosklonny
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D016922:Cellular Senescence / Q000187:drug effects; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D008954:Models, Biological; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*
chemical_list: D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: aging; cancer; cell cycle; growth; rapalogs; senescence
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