Stat3 dimerization regulated by reversible acetylation of a single lysine residue.

Science (New York, N.Y.) ·Vol. 307 ·No. 5707 ·2005-01-14 ·Pages 269-73

Yuan ZL, Guan YJ, Chatterjee D, Chin YE

Abstract

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.

MeSH Terms

Acetylation Acetyltransferases/metabolism Arginine/chemistry,metabolism Cell Cycle Cell Line, Tumor Cell Nucleus/metabolism Cyclin D1/metabolism Cytokines/pharmacology,physiology Cytoplasm/metabolism DNA/metabolism DNA-Binding Proteins/chemistry,genetics,metabolism Dimerization HeLa Cells Histone Acetyltransferases Histone Deacetylases/metabolism Humans Interferon-alpha/pharmacology Lysine/metabolism Mutation Nuclear Proteins/metabolism Oncostatin M Peptides/pharmacology Phosphorylation Protein Structure, Secondary Proto-Oncogene Proteins c-bcl-2/metabolism Proto-Oncogene Proteins c-myc/metabolism Recombinant Fusion Proteins/chemistry,metabolism STAT3 Transcription Factor Signal Transduction Trans-Activators/chemistry,genetics,metabolism Transcriptional Activation bcl-X Protein src Homology Domains

Chemicals

BCL2L1 protein, human Cytokines DNA-Binding Proteins Interferon-alpha MYC protein, human Nuclear Proteins OSM protein, human Peptides Proto-Oncogene Proteins c-bcl-2 Proto-Oncogene Proteins c-myc Recombinant Fusion Proteins STAT3 Transcription Factor STAT3 protein, human Trans-Activators bcl-X Protein Oncostatin M Cyclin D1 DNA Arginine Acetyltransferases Histone Acetyltransferases Histone Deacetylases Lysine

Authors & Affiliations

4 authors, click to expand affiliations / ORCID

Yuan Zheng-Long

Department of Surgery, Brown University Medical School-Rhode Island Hospital, Providence, RI 02903, USA.

Guan Ying-Jie

Chatterjee Devasis

Chin Y Eugene

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

1095-9203

DOI

10.1126/science.1105166

Published

2005-01-14

Pages

269-73

Language

English

Region

United States

NLM ID

0404511

Subset

Corrections

CommentIn

PMID: 15653493

External Links

PubMed source DOI: 10.1126/science.1105166 View journal details

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Stat3 dimerization regulated by reversible acetylation of a single lysine residue.

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