| Literature DB >> 19026785 |
Guang Yang1, Yitang Li, Emi K Nishimura, Hong Xin, Anyu Zhou, Yinshi Guo, Liang Dong, Mitchell F Denning, Brian J Nickoloff, Rutao Cui.
Abstract
The protein encoded by paired-box homeotic gene 3 (PAX3) is a key regulator of the microphthalmia-associated transcription factor (Mitf) in the melanocyte lineage. Here, we show that PAX3 expression in skin is directly inhibited by TGF-beta/Smads. UV irradiation represses TGF-beta in keratinocytes, and the repression of TGF-beta/Smads upregulates PAX3 in melanocytes, which is associated with a UV-induced melanogenic response and consequent pigmentation. Furthermore, the TGF-beta-PAX3 signaling pathway interacts with the p53-POMC/MSH-MC1R signaling pathway, and both are crucial in melanogenesis. The activation of p53-POMC/MSH-MC1R signaling is required for the UV-induced melanogenic response because PAX3 functions in synergy with SOX10 in a cAMP-response element (CRE)-dependent manner to regulate the transcription of Mitf. This study will provide a rich foundation for further research on skin cancer prevention by enabling us to identify targeted small molecules in the signaling pathways of the UV-induced melanogenic response that are highly likely to induce naturally protective pigmentation.Entities:
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Year: 2008 PMID： 19026785 DOI： 10.1016/j.molcel.2008.11.002
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970