Pax3 and regulation of the melanocyte-specific tyrosinase-related protein-1 promoter.

Abstract	Previous work has established that the melanocyte-specific tyrosinase-related protein-1 (TRP-1) promoter is regulated positively by the microphthalmia-associated transcription factor Mitf, acting through the conserved M box and negatively by the T-box factor Tbx2, which can bind two "melanocyte-specific elements" termed the MSEu and MSEi. Both the MSEu and MSEi, which share a 6-base pair GTGTGA consensus, are also recognized by a previously unidentified melanocyte-specific factor, MSF. Here we show using a combination of DNA binding assays, proteolytic clipping, and anti-Pax3 antibodies that MSF is indistinguishable from Pax3, a paired homeodomain transcription factor implicated genetically in melanocyte development and the regulation of the Mitf promoter. Consistent with Pax3 being able to bind the TRP-1 promoter, Pax3 is expressed in melanocytes and melanomas, and TRP-1 promoter activity is up-regulated by Pax3. The results identify a novel role for Pax3 in the expression of TRP-1, and the potential role of Pax3 in the melanocyte lineage is discussed.
Authors	M D Galibert, U Yavuzer, T J Dexter, C R Goding
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 274 Issue 38 Pg. 26894-900 (Sep 17 1999) ISSN: 0021-9258 [Print] United States
PMID	10480898 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	DNA-Binding Proteins Membrane Glycoproteins PAX3 Transcription Factor Paired Box Transcription Factors Proteins Transcription Factors Pax3 protein, mouse Oxidoreductases Tyrp1 protein, mouse tyrosinase-related protein-1
Topics	Animals Base Sequence Cell Differentiation DNA-Binding Proteins (physiology) Gene Expression Regulation Melanocytes (cytology, metabolism) Melanoma (metabolism) Membrane Glycoproteins Mice Molecular Sequence Data Oxidoreductases PAX3 Transcription Factor Paired Box Transcription Factors Promoter Regions, Genetic Proteins (genetics) Transcription Factors Transfection Tumor Cells, Cultured

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