Stat3 dimerization regulated by reversible acetylation of a single lysine residue

Upon cytokine treatment, members of the signal transducers and activators of transcription (STAT) family of proteins are phosphorytated 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, Lys(685). Histone acetyltransferase p300-mediated Stat3 acetylation on Lys(685) was reversible by type I histone deacetylase (HDAC). Use of a prostate cancer cell line (PC3) that lacks Stat3 and PC3 cells expressing wildtype Stat3 or a Stat3 mutant containing a Lys(685)-to-Arg substitution revealed that Lys(685) 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.