Yagil Zohar, Kay Gillian, Nechushtan Hovav, Razin Ehud
Department of Biochemistry, Hebrew University Hadassah Medical School, Jerusalem, Israel.
J Immunol. 2009 Feb 15;182(4):2168-75. doi: 10.4049/jimmunol.0803030.
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.
活化STAT3的蛋白抑制剂(PIAS3)在体内作为一种关键分子,可抑制小眼畸形转录因子(MITF)和STAT3的转录活性,这两种转录因子在肥大细胞和黑素细胞的发育、表型表达及存活中起主要作用。在本研究中,我们探究了PIAS3在肥大细胞和黑素细胞细胞周期调控中所起的作用。我们已对源自PIAS3的一个23个氨基酸的结构域的生物学作用进行了表征,该结构域通过抑制MITF和STAT3的转录活性在这些细胞中诱导凋亡。这种PIAS3抑制肽可作为深入研究开发MITF和STAT3肽抑制剂的开端。