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Upon cytokine treatment, members of the signal transducers andactivators of transcription (STAT) family of proteins are phosphorylatedon tyrosine and serine sites within the carboxyl-terminal regionin cells. We show that in response to cytokine treatment, Stat3is also acetylated on a single lysine residue, Lys685. Histoneacetyltransferase p300–mediated Stat3 acetylation on Lys685was reversible by type I histone deacetylase (HDAC). Use ofa prostate cancer cell line (PC3) that lacks Stat3 and PC3 cellsexpressing wild-type Stat3 or a Stat3 mutant containing a Lys685-to-Argsubstitution revealed that Lys685 acetylation was critical forStat3 to form stable dimers required for cytokine-stimulatedDNA binding and transcriptional regulation, to enhance transcriptionof cell growth–related genes, and to promote cell cycleprogression in response to treatment with oncostatin M.
1 Department of Surgery, Brown University Medical School–Rhode Island Hospital, Providence, RI 02903, USA. 2 Department of Medicine, Brown University Medical School–Rhode Island Hospital, Providence, RI 02903, USA. 3 Department of Molecular Biology, Cell Biology and Biochemistry, Brown University Medical School–Rhode Island Hospital, Providence, RI 02903, USA.
* To whom correspondence should be addressed. E-mail: y_eugene_chin{at}brown.edu
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