Abstract
In the present study, we clarified that transforming growth factor beta (TGF-beta) induces cellular senescence in human normal diploid cells, TIG-1, and identified protein kinase Cs (PKCs) as downstream mediators of TGF-beta-induced cellular senescence. Among PKCs, we showed that PKC-delta induced cellular senescence in TIG-1 cells and was activated in replicatively and prematurely senescent TIG-1 cells. The causative role of PKC-delta in cellular senescence programs was demonstrated using a kinase negative PKC-delta and small interfering RNA against PKC-delta. Furthermore, PKC-delta was shown to function in human telomerase reverse transcriptase (hTERT) gene repression. These results indicate that PKC-delta plays a key role in cellular senescence programs, and suggest that the induction of senescence and hTERT repression are coordinately regulated by PKC-delta.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetamides / pharmacology
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Catalytic Domain / genetics
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Cell Line
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Cell Proliferation / drug effects
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Cellular Senescence / physiology*
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Diploidy
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Enzyme Activators / pharmacology
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Fibroblasts / metabolism
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Fibroblasts / pathology
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Gene Expression Regulation, Enzymologic
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Genes, ras
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Humans
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Kidney / cytology
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Kidney / metabolism
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Protein Kinase C-delta / antagonists & inhibitors
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Protein Kinase C-delta / biosynthesis
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Protein Kinase C-delta / physiology*
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Pyrans / pharmacology
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RNA, Small Interfering
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Recombinant Proteins / biosynthesis
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Spiro Compounds / pharmacology
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Telomerase / genetics
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Transduction, Genetic
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Transforming Growth Factor beta / pharmacology
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beta-Galactosidase / biosynthesis
Substances
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Acetamides
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Enzyme Activators
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Pyrans
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RNA, Small Interfering
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Recombinant Proteins
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Spiro Compounds
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Transforming Growth Factor beta
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bistratene A
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PRKCD protein, human
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Protein Kinase C-delta
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TERT protein, human
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Telomerase
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beta-Galactosidase