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Science 14 January 2005:
Vol. 307. no. 5707, pp. 269 - 273
DOI: 10.1126/science.1105166
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Reports

Stat3 Dimerization Regulated by Reversible Acetylation of a Single Lysine Residue

Zheng-long Yuan,1,3 Ying-jie Guan,1,3 Devasis Chatterjee,2 Y. Eugene Chin1,3*

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.

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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