Protein kinase C δ plays a key role in cellular senescence programs of human normal diploid cells

In the present study, we clarified that transforming growth factor β (TGF-β) induces cellular senescence in human normal diploid cells, TIG-1, and identified protein kinase Cs (PKCs) as downstream mediators of TGF-β-induced cellular senescence. Among PKCs, we showed that PKC-δ induced cellular senescence in TIG-1 cells and was activated in replicatively and prematurely senescent TIG-1 cells. The causative role of PKC-δ in cellular senescence programs was demonstrated using a kinase negative PKC-δ and small interfering RNA against PKC-δ. Furthermore, PKC-δ was shown to function in human telomerase reverse transcriptase (hTERT) gene repression. These results indicate that PKC-δ plays a key role in cellular senescence programs, and suggest that the induction of senescence and hTERT repression are coordinately regulated by PKC-δ.