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.
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STAT3 activity can be modified by reversible acetylation of lysine 685 (K685), which is critical for the formation of stable STAT3 dimers and is required for cytokine-induced STAT3-mediated transcription.
“In addition, STAT3 activity can be modified by reversible acetylation of lysine 685 (K685), an event that is critical for the formation of stable STAT3 dimers and is required for cytokine-induced STAT3-mediated transcription.11,12”
From Critical analysis of the potential for targeting STAT3 in human malignancy (2013) · cites this paper as [12]
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“In addition, STAT3 activity can be modified by reversible acetylation of lysine 685 (K685), an event that is critical for the formation of stable STAT3 dimers and is required for cytokine-induced STAT3-mediated transcription.(11,12) Downregulation of STAT3 occurs by several mechanisms in normal biology.”
- Authors
- Yuan, Z.-L., Guan, Y.-J., Chatterjee, D., & Chin, Y. E.
- Affiliations
- Department of Surgery, Brown University Medical School–Rhode Island Hospital, Providence, RI 02903, USA.
- Brown University (US)
- Corresponding author
- Chin, Y. Eugene
- ORCID
- Chin, Y. Eugene
- Venue
- Science
- Published
- 2005-01-14
- Volume
- 307
- Issue
- 5707
- Pages
- 269-273
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2072669480
- Cited by
- 790
- References
- 1
- Citations by year
- 2026: 28 · 2025: 29 · 2024: 22 · 2023: 29 · 2022: 28 · 2021: 34 · 2020: 25 · 2019: 37 · 2018: 47 · 2017: 37 · 2016: 48 · 2015: 42 · 2014: 52 · 2013: 59 · 2012: 47
- FWCI
- 18.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Keywords
- STAT3, protein acetylation, lysine acetylation, STAT3 dimerization, P300, histone deacetylase, cytokine signaling, transcriptional regulation, oncostatin M, cell cycle progression, prostate cancer, DNA binding
- MeSH terms
- Acetylation, Acetyltransferases, Arginine, Cell Cycle, Cell Nucleus, Cytoplasm, DNA, DNA-Binding Proteins, HeLa Cells, Histone Deacetylases, Humans, Lysine, Mutation, Nuclear Proteins, Peptides, Phosphorylation, Recombinant Fusion Proteins, Signal Transduction, Transcriptional Activation, Trans-Activators, Cytokines, Proto-Oncogene Proteins c-myc, Interferon-alpha, Protein Structure, Secondary, src Homology Domains, Proto-Oncogene Proteins c-bcl-2, Dimerization, Cyclin D1, Cell Line, Tumor, STAT3 Transcription Factor, bcl-X Protein, Histone Acetyltransferases, Oncostatin M
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