TGF-beta1 induction of p21WAF1/cip1 requires smad-independent protein kinase C signaling pathway.
Although it has been demonstrated that p21WAF1/Cip1 could be induced by transforming growth factor-beta1 (TGF-beta1) in a Smad-dependent manner, the cross-talk of Smad signaling pathway with other signaling pathways still remains poorly understood. In this study, we investigated a possible role of protein kinase C (PKC) signaling pathway in TGF-beta1 induction of p21WAF1/Cip1 in human keratinocytes HaCaT cells. Our data show that PKC is required for TGF-beta1 induction of p21WAF1/Cip1, as evidenced by the fact that specific inhibition of PKC leads to a decrease in p21WAF1/Cip1 protein and mRNA expression induced by TGF-beta1. And this notion is further supported by the observation that activation of p21WAF1/Cip1 promoter activity is dramatically attenu ated by treatment with PKC inhibitor. However, PKC signaling pathway is not associated with TGF-beta1 activation of Smad signaling pathway, because inhibition of PKC signaling pathway does not affect nuclear translocation of Smads induced by TGF-beta1. Taken together, our data suggest that PKC signaling pathway is required for p21WAF1/Cip1 expression by TGF-beta1, which is independent of Smad signaling pathway.
Department of Pharmacology, Kwandong University College of Medicine, Gangneung 210-701, Korea. yksnbk@kwandong.ac.kr
Yong Kee
YK
Kim
D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D017930:Genes, Reporter / Q000235:genetics; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D009281:Naphthalenes / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014404:Tubulin / Q000096:biosynthesis
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009281:Naphthalenes; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D014404:Tubulin; D015240:Phorbol 12,13-Dibutyrate; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D011493:Protein Kinase C; C058819:calphostin C; D004121:Dimethyl Sulfoxide