Stat3 Dimerization Regulated by Reversible Acetylation of a Single Lysine Residue

作者：Zhenglong Yuan, Yingjie A. Guan, Devasis Chatterjee, Yue Eugene Chin · 发表于：Science · 年份：2005 · DOI：10.1126/science.1105166 · 被引用次数：800 · 研究领域：Cytokine Signaling Pathways and Interactions、NF-κB Signaling Pathways、Genomics, phytochemicals, and oxidative stress

Upon cytokine treatment, members of the signal transducers and activators of transcription (STAT) family of proteins are phosphorylated on tyrosine and serine sites within the carboxyl-terminal region in cells. We show that in response to cytokine treatment, Stat3 is also acetylated on a single lysine residue, Lys685. Histone acetyltransferase p300-mediated Stat3 acetylation on Lys685 was reversible by type I histone deacetylase (HDAC). Use of a prostate cancer cell line (PC3) that lacks Stat3 and PC3 cells expressing wild-type Stat3 or a Stat3 mutant containing a Lys685-to-Arg substitution revealed that Lys685 acetylation was critical for Stat3 to form stable dimers required for cytokine-stimulated DNA binding and transcriptional regulation, to enhance transcription of cell growth-related genes, and to promote cell cycle progression in response to treatment with oncostatin M.