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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.

Type

Journal article

Journal

J Biol Chem

Publication Date

17/09/1999

Volume

274

Pages

26894 - 26900

Keywords

Animals, Base Sequence, Cell Differentiation, DNA-Binding Proteins, Gene Expression Regulation, Melanocytes, Melanoma, Membrane Glycoproteins, Mice, Molecular Sequence Data, Oxidoreductases, PAX3 Transcription Factor, Paired Box Transcription Factors, Promoter Regions, Genetic, Proteins, Transcription Factors, Transfection, Tumor Cells, Cultured