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.
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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)
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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
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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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