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Regulations of Reversal of Senescence by PKC Isozymes in Response to 12-O-Tetradecanoylphorbol-13-Acetate via Nuclear Translocation of pErk1/2
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  • Journal title : Molecules and Cells
  • Volume 39, Issue 3,  2016, pp.266-279
  • Publisher : Korea Society for Molecular and Cellular Biology
  • DOI : 10.14348/molcells.2016.2362
 Title & Authors
Regulations of Reversal of Senescence by PKC Isozymes in Response to 12-O-Tetradecanoylphorbol-13-Acetate via Nuclear Translocation of pErk1/2
Lee, Yun Yeong; Ryu, Min Sook; Kim, Hong Seok; Suganuma, Masami; Song, Kye Yong; Lim, In Kyoung;
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 Abstract
The mechanism by which 12-O-tetradecanoylphorbol-13-acetate (TPA) bypasses cellular senescence was investigated using human diploid fibroblast (HDF) cell replicative senescence as a model. Upon TPA treatment, protein kinase C (PKC) and exerted differential effects on the nuclear translocation of cytoplasmic pErk1/2, a protein which maintains senescence. accompanied pErk1/2 to the nucleus after freeing it from via and then was rapidly ubiquitinated and degraded within the nucleus. Mitogen-activated protein kinase docking motif and kinase activity of were both required for pErk1/2 transport to the nucleus. Repetitive exposure of mouse skin to TPA downregulated expression and increased epidermal and hair follicle cell proliferation. Thus, downregulation is accompanied by in vivo cell proliferation, as evidenced in 7, 12-dimethylbenz(a)anthracene (DMBA)-TPA-mediated carcinogenesis. The ability of TPA to reverse senescence was further demonstrated in old HDF cells using RNA-sequencing analyses in which TPA-induced nuclear degradation freed nuclear pErk1/2 to induce cell proliferation and facilitated the recovery of mitochondrial energy metabolism. Our data indicate that TPA-induced senescence reversal and carcinogenesis promotion share the same molecular pathway. Loss of expression following TPA treatment reduces pErk1/2-activated SP1 biding to the gene promoter, thus preventing senescence onset and overcoming G1/S cell cycle arrest in senescent cells.
 Keywords
HDF;;;SA-pErk1/2;tumor promotion;
 Language
English
 Cited by
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Survive or thrive: tradeoff strategy for cellular senescence, Experimental & Molecular Medicine, 2017, 49, 6, e342  crossref(new windwow)
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