title: Stat3 dimerization regulated by reversible acetylation of a single lysine residue.
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.
authors.affiliation: Department of Surgery, Brown University Medical School-Rhode Island Hospital, Providence, RI 02903, USA.
authors.forename: Zheng-Long
authors.initials: ZL
authors.lastname: Yuan
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Guan
authors.forename: Devasis
authors.initials: D
authors.lastname: Chatterjee
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chin
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D001120:Arginine / Q000737:chemistry / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D008239:Lysine / Q000378:metabolism*; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation; D017433:Protein Structure, Secondary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D051020:bcl-X Protein; D018909:src Homology Domains
chemical_list: C494811:BCL2L1 protein, human; D016207:Cytokines; D004268:DNA-Binding Proteins; D016898:Interferon-alpha; C489427:MYC protein, human; D009687:Nuclear Proteins; C508351:OSM protein, human; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D051020:bcl-X Protein; D053683:Oncostatin M; D019938:Cyclin D1; D004247:DNA; D001120:Arginine; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases; D008239:Lysine