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-associated transcription factor (Mitf) is essential for melanocytic lineage development and for expression of melanogenic enzymes, such as tyrosinase. Interleukin-6 receptor/interleukin-6 chimera (IL6RIL6) induces in B16/F10.9 melanoma cells a loss of melanogenesis preceded by a sharp decrease in Mitf mRNA and gene promoter activity. In the Mitf promoter, the main cis-acting element mediating the IL6RIL6 effect is shown to be the binding site of Pax3, a paired homeodomain factor regulating among other things the development of melanocytes. Pax3 protein and mRNA levels decline steadily after IL6RIL6 treatment, and overexpression of an ectopic Pax3 cDNA suppresses the Mitf promoter inhibition. Loss of the synergism between Pax3 and Sox10, a high mobility group domain costimulatory factor, seems to be critical in the rapid decrease in Mitf gene expression. The Pax3 down-regulation in IL6RIL6-induced F10.9 cell is linked to growth arrest and transdifferentiation to a glial cell phenotype. IL6RIL6 stimulates the interleukin-6 family cytokine receptor gp130, leading to the rapid phosphorylation of Stat3 on tyrosine 705. This phosphorylation is required for Pax3 down-regulation and Mitf promoter silencing since these are inhibited in F10.9 cells overexpressing the Stat3 DN-mutant Y705F.
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PMID:Pax3 down-regulation and shut-off of melanogenesis in melanoma B16/F10.9 by interleukin-6 receptor signaling. 1183 May 92

We previously reported that antigen expression in melanoma cell lines is down-regulated by proteins secreted by antigen-negative melanoma cells. Here we report the purification and characterization of one of these down-regulatory factors, the cytokine, oncostatin M (OSM), which transmits its signal via the gp130 cell surface receptor, resulting in the selective down-modulation of the melanocyte lineage antigens: Melan-A/MART-1, gp100, tyrosinase, tyrosinase-related proteins 1 and 2, and the M isoform of microphthalmia transcription factor. Furthermore, we have found that some melanoma cell lines produce as yet uncharacterized factors distinct from OSM which also down-modulate antigen expression via signaling pathways different from that employed by OSM. These data indicate that there may be several regulatory pathways and molecules involved in the antigen-silencing process which may be related to the state of differentiation of the tumor cell and may affect the outcome of antitumor vaccine immunotherapies.
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PMID:Induction of "antigen silencing" in melanomas by oncostatin M: down-modulation of melanocyte antigen expression. 1269 60