Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Regulation of melanocyte pivotal transcription factor MITF by some other transcription factors. 2151 23

PAX3 (paired box 3) is known to have an important role in melanocyte development through modulation of microphthalmia-associated transcription factor transcription. Here we found that PAX3 transcriptional activity could be regulated through FGF2 (basic fibroblast growth factor)-STAT3 (signal transducer and activator of transcription 3) signaling in the pigment cells. To study its function in vivo, we have generated a transgenic mouse model expressing PAX3 driven by tyrosinase promoter in a tissue-specific fashion. These animals exhibit hyperpigmentation in the epidermis, evident in the skin color of their ears and tails. We showed that the darker skin color results from both increased melanocyte numbers and melanin synthesis. Together, our study delineated a novel pathway in the melanocyte lineage, linking FGF2-STAT3 signaling to increased PAX3 transcription. Moreover, our results suggest that this pathway might contribute to the regulation of melanocyte numbers and melanin levels, and thereby provide an alternative strategy to induce pigmentation.
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PMID:FGF2 regulates melanocytes viability through the STAT3-transactivated PAX3 transcription. 2199 91