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
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Acetylation
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Acetyltransferases / metabolism
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Arginine / chemistry
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Arginine / metabolism
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Cell Cycle
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Cell Line, Tumor
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Cell Nucleus / metabolism
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Cyclin D1 / metabolism
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Cytokines / pharmacology
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Cytokines / physiology*
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Cytoplasm / metabolism
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DNA / metabolism
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Dimerization
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HeLa Cells
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Histone Acetyltransferases
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Histone Deacetylases / metabolism
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Humans
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Interferon-alpha / pharmacology
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Lysine / metabolism*
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Mutation
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Nuclear Proteins / metabolism
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Oncostatin M
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Peptides / pharmacology
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Phosphorylation
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Protein Structure, Secondary
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Proto-Oncogene Proteins c-myc / metabolism
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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STAT3 Transcription Factor
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Signal Transduction*
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Trans-Activators / chemistry
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcriptional Activation
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bcl-X Protein
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src Homology Domains
Substances
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BCL2L1 protein, human
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Cytokines
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DNA-Binding Proteins
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Interferon-alpha
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MYC protein, human
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Nuclear Proteins
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OSM protein, human
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Peptides
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Proto-Oncogene Proteins c-bcl-2
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Proto-Oncogene Proteins c-myc
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Recombinant Fusion Proteins
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STAT3 Transcription Factor
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STAT3 protein, human
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Trans-Activators
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bcl-X Protein
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Oncostatin M
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Cyclin D1
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DNA
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Arginine
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Acetyltransferases
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Histone Acetyltransferases
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Histone Deacetylases
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Lysine