Stat3 Dimerization Regulated by Reversible Acetylation of a Single Lysine Residue

• Published in: Science (American Association for the Advancement of Science) Vol. 307; no. 5707; pp. 269 - 273
• Main Authors: Yuan, Zheng-long, Guan, Ying-jie, Chatterjee, Devasis, Chin, Y. Eugene
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 14.01.2005; The American Association for the Advancement of Science
• Subjects: Acetylation; Acetyltransferases - metabolism; Antibodies; Arginine - chemistry; Arginine - metabolism; bcl-X Protein; Biological and medical sciences; Cell Cycle; Cell growth; Cell Line, Tumor; Cell lines; Cell Nucleus - metabolism; Cell physiology; Cells; COS cells; Cyclin D1 - metabolism; Cytokines; Cytokines - pharmacology; Cytokines - physiology; Cytoplasm - metabolism; Deoxyribonucleic acid; Dimerization; Dimers; DNA; DNA - metabolism; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Fractions; Fundamental and applied biological sciences. Psychology; Gene expression; HeLa Cells; Histone Acetyltransferases; Histone Deacetylases - metabolism; Humans; Interferon-alpha - pharmacology; Lysine - metabolism; Medical treatment; Molecular and cellular biology; Mutation; Nuclear Proteins - metabolism; Oncostatin M; Peptides - pharmacology; Phosphorylation; Prostate cancer; Protein Structure, Secondary; Proteins; Proto-Oncogene Proteins c-bcl-2 - metabolism; Proto-Oncogene Proteins c-myc - metabolism; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - metabolism; Signal Transduction; src Homology Domains; STAT3 Transcription Factor; Trans-Activators - chemistry; Trans-Activators - genetics; Trans-Activators - metabolism; Transcriptional Activation; Signal transduction; Urinary system disease; Treatment; Prostate disease; Cytokine; Transcription factor STAT3; Malignant tumor; Acetylation; Male genital diseases; Dimerization
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1105166

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.