Cellular senescence plays a key role in complicated biological processes, including development, aging, and tumorigenesis. Hallmarks of cellular senescence are metabolically active but not responsive to mitogens, therefore, decreased cell growth, cell cycle arrest, and reached to the flat and large cell shapes. We have recently reported that high expression of senescence-associated p-extracellular signal-regulated protein kinase 1/2 (SA-pErk1/2) can induce p21WAF1 expression via the activation of a transcription factor, SP1. In the present work, we investigated a biochemical regulation of the cytoplasmic sequestration of SA-pErk1/2 and found that PEA-15 (phosphoprotein enriched in astrocytes-15) could regulate translocation of SA-pErk1/2 to nuclei along with activation of PKC-α in senescent cells. It was proved by treatment of senescent cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), which phosphorylated PEA-15 upon Ser104 residue via activation of PKC-α, which lead to release of SA-pErk1/2 form PEA-15 and then accompanied with nuclear translocation of SA-pErk1/2 along with PKC-α. Here, we, report the mechanism of cytoplasmic sequestration of SA-pErk1/2 and the relationship between PEA-15 and PKC-α in senescent human diploid fibroblasts (HDFs).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3217.
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