A specific epitope of protein inhibitor of activated STAT3 is responsible for the induction of apoptosis in rat transformed mast cells.
Protein inhibitor of activated STAT3 (PIAS3) functions in vivo as a key molecule in suppressing the transcriptional activity of both microphthalmia transcription factor (MITF) and STAT3, two transcription factors that play a major role in the development, phenotypic expression, and survival of mast cells and melanocytes. In the present study we have investigated the role played by PIAS3 in the regulation of cell cycle in mast cells and melanocytes. We have characterized the biological role of a 23-aa domain derived from PIAS3 that induces apoptosis in these cells by inhibiting the transcriptional activity of both MITF and STAT3. This PIAS3 inhibitor peptide could serve as the beginning of an in depth study for the development of peptide inhibitors for MITF and STAT3.
Yagil
Zohar
Z
Department of Biochemistry, Hebrew University Hadassah Medical School, Jerusalem, Israel.
Kay
Gillian
G
Nechushtan
Hovav
H
Razin
Ehud
E
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D000939:Epitopes / Q000737:chemistry / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000502:physiology*; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology*; D008546:Melanoma, Experimental / Q000473:pathology; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism; D050828:Protein Inhibitors of Activated STAT / Q000737:chemistry* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D000939:Epitopes; D051739:Microphthalmia-Associated Transcription Factor; D018832:Molecular Chaperones; C112253:Pias3 protein, rat; D050828:Protein Inhibitors of Activated STAT; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; D053148:Caspase 3