Stat3 dimerization regulated by reversible acetylation of a single lysine residue

Science. 2005 Jan 14;307(5707):269-73. doi: 10.1126/science.1105166.

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
  • Arginine / metabolism
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cyclin D1 / metabolism
  • Cytokines / pharmacology
  • Cytokines / physiology*
  • Cytoplasm / metabolism
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / 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
  • Recombinant Fusion Proteins / metabolism
  • STAT3 Transcription Factor
  • Signal Transduction*
  • Trans-Activators / chemistry
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcriptional Activation
  • bcl-X Protein
  • src Homology Domains

Substances

  • 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