Stat3 Dimerization Regulated by Reversible Acetylation of a Single Lysine Residue
2005/01/13 by Zheng-long Yuan, Zhenglong Yuan, Ying-jie Guan +3 · 29 citations
Medicine · Biochemistry, Genetics and Molecular Biology · #Cytokine Signaling Pathways and Interactions #NF-κB Signaling Pathways #Genomics, phytochemicals, and oxidative stress
paper · 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.
Cited by
- The nuclear factor- B-interleukin-6 signalling pathway mediating vascular inflammation
- EGF receptor trafficking: consequences for signaling and cancer
- Glucose Metabolism as a Target of Histone Deacetylase Inhibitors
- NF-κB and STAT3 – key players in liver inflammation and cancer
- A positive autoregulatory loop of Jak-STAT signaling controls the onset of astrogliogenesis. [europepmc]
- RNA interference-directed knockdown of urokinase plasminogen activator and urokinase plasminogen activator receptor inhibits prostate cancer cell invasion, survival, and tumorigenicity in vivo. [europepmc]
- Lysine acetylation: codified crosstalk with other posttranslational modifications. [europepmc]
- STAT3 inhibition of gluconeogenesis is downregulated by SirT1. [europepmc]
- Signal transducer and activator of transcription-3, inflammation, and cancer: how intimate is the relationship?. [europepmc]
- Cross-regulation of signaling pathways by interferon-gamma: implications for immune responses and autoimmune diseases. [europepmc]
- Dangerous liaisons: STAT3 and NF-kappaB collaboration and crosstalk in cancer. [europepmc]
- The nuclear factor-kappaB-interleukin-6 signalling pathway mediating vascular inflammation. [europepmc]
- Nonhistone protein acetylation as cancer therapy targets. [europepmc]
- NF-κB and STAT3 - key players in liver inflammation and cancer. [europepmc]
- Biology and significance of the JAK/STAT signalling pathways. [europepmc]
- The JAK-STAT pathway at twenty. [europepmc]
- The involvement of the JAK-STAT signaling pathway in chronic inflammatory skin disease atopic dermatitis. [europepmc]
- STAT3 signaling in immunity. [europepmc]
- HDAC Inhibitors as Epigenetic Regulators of the Immune System: Impacts on Cancer Therapy and Inflammatory Diseases. [europepmc]
- The role of STAT3 in leading the crosstalk between human cancers and the immune system. [europepmc]
- Lysine Acetylation Goes Global: From Epigenetics to Metabolism and Therapeutics. [europepmc]
- Implications of STAT3 and STAT5 signaling on gene regulation and chromatin remodeling in hematopoietic cancer. [europepmc]
- Acetylation Blocks cGAS Activity and Inhibits Self-DNA-Induced Autoimmunity. [europepmc]
- Modulation of M2 macrophage polarization by the crosstalk between Stat6 and Trim24. [europepmc]
- Role of JAK/STAT3 Signaling in the Regulation of Metastasis, the Transition of Cancer Stem Cells, and Chemoresistance of Cancer by Epithelial-Mesenchymal Transition. [europepmc]
- Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution. [europepmc]
- A STAT3 palmitoylation cycle promotes T H 17 differentiation and colitis. [europepmc]
- Loss of fatty acid degradation by astrocytic mitochondria triggers neuroinflammation and neurodegeneration. [europepmc]
- Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications. [europepmc]
Related