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KMID : 0043320070300060739
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Archives of Pharmacal Research
2007 Volume.30 No. 6 p.739 ~ p.742
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TGF-β1 Induction of p21WAF1/Cip1 Requires Smad-Independent Protein Kinase C Signaling Pathway
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Kim Yong-Kee
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Abstract
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Although it has been demonstrated that p21WAF1/Cip1 could be induced by transforming growth factor-β1 (TGF-β1) 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-β1 induction of p21WAF1/Cip1 in human keratinocytes HaCaT cells. Our data show that PKC is required for TGF-β1 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-β1. And this notion is further supported by the observation that activation of p21WAF1/Cip1 promoter activity is dramatically attenuated by treatment with PKC inhibitor. However, PKC signaling pathway is not associated with TGF-β1 activation of Smad signaling pathway, because inhibition of PKC signaling pathway does not affect nuclear translocation of Smads induced by TGF-β1. Taken together, our data suggest that PKC signaling pathway is required for p21WAF1/Cip1 expression by TGF-β1, which is independent of Smad signaling pathway.
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KEYWORD
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TGF-β, p21WAF1/Cip1, PKC, Smads
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