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 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.