Protein kinase C delta plays a key role in cellular senescence programs of human normal diploid cells.
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.
Katakura
Yoshinori
Y
Department of Genetic Resources Technology, Kyushu University, Fukuoka, Japan. katakura@grt.kyushu-u.ac.jp
Udono
Miyako
M
Katsuki
Kazuyuki
K
Nishide
Hisaya
H
Tabira
Yukiko
Y
Ikei
Takahiro
T
Yamashita
Makiko
M
Fujiki
Tsukasa
T
Shirahata
Sanetaka
S
D000081:Acetamides / Q000494:pharmacology; D020134:Catalytic Domain / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000502:physiology*; D004171:Diploidy; D020536:Enzyme Activators / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D011905:Genes, ras; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D011714:Pyrans / Q000494:pharmacology; D034741:RNA, Small Interfering; D011994:Recombinant Proteins / Q000096:biosynthesis; D013141:Spiro Compounds / Q000494:pharmacology; D019098:Telomerase / Q000235:genetics; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D001616:beta-Galactosidase / Q000096:biosynthesis
D000081:Acetamides; D020536:Enzyme Activators; D011714:Pyrans; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D013141:Spiro Compounds; D016212:Transforming Growth Factor beta; C059975:bistratene A; C497258:PRKCD protein, human; D051745:Protein Kinase C-delta; C509186:TERT protein, human; D019098:Telomerase; D001616:beta-Galactosidase