Regulation of melanocyte pivotal transcription factor MITF by some other transcription factors

Abstract

The microphthalmia transcription factor (MITF) is discussed as the master gene for melanocytic survival and a key transcription factor regulating the expression of tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2). MITF is influenced in a complex manner by a large number of different extracellular and intracellular proteins. Many transcription factors are able to modulate the expression and/or transcriptional activity of MITF in vivo. In this review, we summarize these transcription factors that regulate MITF and their interactions. The Sry-related HMG box 10 (SOX10) can directly transactivate the MITF gene and cooperate with MITF to activate TRP-2 expression. The Paired box 3 (PAX3) can increase MITF expression by binding to its promoter and simultaneously prevent MITF from activating downstream genes by competition for enhancer occupancy. Activated signal transducer and activator of transcription 3 (STAT3) and protein inhibitor of activated STAT3 (PIAS3) are able to regulate transcriptional activity of MITF through their interaction. Activated cAMP response element binding protein (CREB) can bind the cAMP response element to increase the MITF gene expression. MITF expression can also be initiated by lymphoid-enhancing factor-1 (LEF-1) and be temporally facilitated by the synergy of LEF-1 and MITF. Both immunoglobulin transcription factor-2 (ITF2) and forkhead-box transcription factor D3 (FOXD3) can negatively regulate MITF expression. All the above-mentioned transcription factors constitute a regulatory network that precisely modulates the MITF.