Activation of Stat3 Sequence-specific DNA Binding and Transcription by p300/CREB-binding Protein-mediated Acetylation
Open accessAbstract
Signal transducers and activators of transcription (Stat) belong to a family of latent cytoplasmic factors that can be activated by tyrosine phosphorylation by members of the Jak tyrosine kinase family in response to a variety of cytokines and growth factors. Activated Stats form dimers and translocate into nucleus to induce expression of critical genes essential for normal cellular events. Here we report for the first time that Stat3 can be modified by acetylation both in vivo and in vitro. A major site of Stat3 that is acetylated by its coactivator, p300/CREB-binding protein (CBP), resides in the C-terminal transcriptional activation domain at lysine 685. Furthermore, the acetylation of Stat3 can stimulate its sequence-specific DNA binding ability and transactivation activity. Inhibition of histone deacetylase activity in cells results in increased Stat3 nuclear localization. These observations clearly indicate a novel mechanism for Stat3 activation in mammalian cells.
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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 [11]
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“K685 acetylation is reported to enhance DNA binding, transactivation activity, and nuclear localization of STAT3 (Ray et al., 2002; Wang et al., 2005), although the conclusion that K685 is important for stable STAT3 dimer formation has been questioned based on structural considerations (O’Shea et…”
BackgroundDong, J., Cheng, X.-D., Zhang, W.-D., & Qin, J.-J. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00629 · Cited by 232 · see citing works
SIRT1 Regulates UV-Induced DNA Repair through Deacetylating XPA
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Self-citationThe complex STATes of astrocyte reactivity: How are they controlled by the JAK-STAT3 pathway?
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Critical analysis of the potential for targeting STAT3 in human malignancy
Grandis, J., & Peyser (2013) · OncoTargets and Therapy · doi:10.2147/ott.s47903 · Cited by 24 · see citing works
“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
- Wang, R., Cherukuri, P., & Luo, J.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Luo, Jianyuan
- ORCID
- Luo, Jianyuan
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-03
- Volume
- 280
- Issue
- 12
- Pages
- 11528-11534
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2073189570
- Cited by
- 275
- References
- 1
- Citations by year
- 2026: 11 · 2025: 10 · 2024: 13 · 2023: 9 · 2022: 8 · 2021: 13 · 2020: 18 · 2019: 15 · 2018: 15 · 2017: 11 · 2016: 14 · 2015: 15 · 2014: 18 · 2013: 10 · 2012: 18
- FWCI
- 6.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship@UMassChan (submittedVersion)
- 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 › Cancer Research › NF-κB Signaling Pathways
- Keywords
- STAT3, acetylation, transactivation domain, sequence-specific DNA binding, transcriptional activation, histone deacetylase inhibition, nuclear localization, transcriptional coactivator
- MeSH terms
- Acetylation, Cells, Cultured, DNA, DNA-Binding Proteins, Humans, Nuclear Proteins, Transcription, Genetic, Trans-Activators, Active Transport, Cell Nucleus, STAT3 Transcription Factor
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