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MITF (microphthalmia-associated transcription factor) is a melanocytic nuclear protein that contains basic helix-loop-helix (HLH) and leucine zipper (LZ) domains. These protein motifs are frequently observed in other transcription factors and are particularly common to members of the Myc family. MITF can directly associate with DNA as a homodimer and is required for the development and differentiation of melanocytes. Its expression is upregulated by cAMP and cAMP-dependent pathways. MITF activates several different gene promoters by binding to their E-boxes. Tyrosinase, TRP1 and TRP2 are pigment synthesis genes activated by MITF. When MITF is phosphorylated on Ser73 (via the MAPK pathway), it associates with co-activators of the p300/CBP family and enhances transcription. MITF has several isoforms including MITF-M which is specifically expressed in melanocytes. In MITFdeficient mice there is a complete absence of melanocytes.
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