Interplay between MITF, PIAS3, and STAT3 in mast cells and melanocytes.
Microphthalmia transcription factor (MITF) and STAT3 are two transcription factors that play a major role in the regulation of growth and function in mast cells and melanocytes. In the present study, we explored the MITF-PIAS3-STAT3 network of interactions, how these interactions regulate gene expression, and how cytokine-mediated phosphorylation of MITF and STAT3 is involved in the in vivo interplay between these three proteins. In NIH 3T3 cells stimulated via gp130 receptor, transfected MITF was found to be phosphorylated at S409. Such phosphorylation of MITF leads to PIAS3 dissociation from MITF and its association with STAT3. Activation of mouse melanoma and mast cells through gp130 or c-Kit receptors induced the mobilization of PIAS3 from MITF to STAT3. In mast cells derived from MITF(di/di) mice, whose MITF lacks the Zip domain (PIAS3-binding domain), we found downregulation in mRNA levels of genes regulated by either MITF or STAT3. This regulatory mechanism is of considerable importance since it is likely to advance the deciphering of a role for MITF and STAT3 in mast cells and melanocytes.
Sonnenblick
Amir
A
Department of Biochemistry, Hebrew University Hadassah Medical School, POB 12272, Jerusalem 91120, Israel.
Levy
Carmit
C
Razin
Ehud
E
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D005456:Fluorescent Dyes; D005982:Glutathione Transferase / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D008407:Mast Cells / Q000378:metabolism*; D008544:Melanocytes / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D051739:Microphthalmia-Associated Transcription Factor; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011233:Precipitin Tests; D050828:Protein Inhibitors of Activated STAT; D017434:Protein Structure, Tertiary; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012235:Rhodamines; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
D004268:DNA-Binding Proteins; C498805:Elp2 protein, mouse; D005456:Fluorescent Dyes; D047908:Intracellular Signaling Peptides and Proteins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; C109279:Pias3 protein, mouse; D050828:Protein Inhibitors of Activated STAT; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D011994:Recombinant Proteins; D012235:Rhodamines; D014157:Transcription Factors; C456339:cytokine receptor, GLM-R; D012694:Serine; D005982:Glutathione Transferase; D019009:Proto-Oncogene Proteins c-kit