Cooperative transcriptional activity of Jun and Stat3 beta, a short form of Stat3.
Open accessAbstract
To identify proteins that regulate the transcriptional activity of c-Jun, we have used the yeast two-hybrid screen to detect mammalian polypeptides that might interact functionally with the N-terminal segment of c-Jun, a known regulatory region. Among the proteins identified is a short form of Stat3 (designated Stat3 beta). Stat3 beta is missing the 55 C-terminal amino acid residues of the long form (Stat3 alpha) and has 7 additional amino acid residues at its C terminus. In the absence of added cytokines, expression of Stat3 beta (but not Stat3 alpha) in transfected cells activated a promoter containing the interleukin 6 responsive element of the rat alpha 2-macroglobulin gene; coexpression of Stat3 beta and c-Jun led to enhanced cooperative activation of the promoter. Nuclear extracts of cells transfected with a Stat3 beta expression plasmid formed a complex with an oligonucleotide containing a Stat3 binding site, whereas extracts of cells transfected with a Stat3 alpha plasmid did not. We conclude that there is a short form of Stat3 (Stat3 beta), that Stat3 beta is transcriptionally active under conditions where Stat3 alpha is not, and that Stat3 beta and c-Jun are capable of cooperative activation of certain promoters.
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Initial support for STAT3β acting as a dominant-negative regulator came with the repression and/or down-regulation of a number of recognized STAT3α target genes when STAT3β was overexpressed.
“Initial support for this came with the repression and/or down-regulation of a number of recognized STAT3α target genes when STAT3β was overexpressed [10,48].”
From Selective STAT3-α or -β expression reveals spliceform-specific phosphorylation kinetics, nuclear retention and distinct gene expression outcomes (2012) · cites this paper as [48]
The Results report that overexpressed STAT3β stimulated the α2-macroglobulin–TK promoter; STAT3α, not STAT3β, slightly repressed reporter expression. The Discussion likewise describes STAT3β as activating this promoter, rather than acting as a dominant-negative regulator. Our copy does not report down-regulation of multiple STAT3α target genes by STAT3β. (LLM, conf=0.85)
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Experimental — accuracy not yet measuredAlthough STATs bind a similar DNA binding site, they may interact with co-activators or co-repressors to regulate different sets of their own downstream targets.
“Although they bind to a similar DNA binding site, STATs may interact with co-activator or co-repressor to regulate different sets of their own downstream targets (5”
From STAT3 Contributes to the Mitogenic Response of Hepatocytes during Liver Regeneration (2002) · cites this paper as [40]
The Discussion (page not provided) reports cooperative activation of a promoter by Stat3β and c-Jun and suggests this could matter for responses involving other STAT proteins. It does not establish that STATs generally bind similar DNA sites or interact with co-repressors to regulate different sets of downstream targets. The similar-site discussion in the introduction concerns Jun and Fos proteins, not STATs. (LLM, conf=0.84)
Experimental — accuracy not yet measured
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Cites
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- Authors
- Schaefer, T. S., Sanders, L. K., & Nathans, D.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1995-09-26
- Volume
- 92
- Issue
- 20
- Pages
- 9097-9101
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC40931
- OpenAlex
- W1974968368
- Cited by
- 357
- References
- 1
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 10 · 2022: 3 · 2021: 6 · 2020: 4 · 2019: 7 · 2018: 7 · 2017: 6 · 2016: 6 · 2015: 8 · 2014: 7 · 2013: 7 · 2012: 11
- FWCI
- 12.29
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (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 › Cancer Research › NF-κB Signaling Pathways
- Keywords
- c-Jun, short isoform, transcription factor interaction, STAT3 binding sites, promoter activation
- MeSH terms
- alpha-Macroglobulins, Amino Acid Sequence, Animals, Base Sequence, Binding Sites, DNA-Binding Proteins, Mammals, Molecular Sequence Data, Oligodeoxyribonucleotides, Promoter Regions, Genetic, Recombinant Proteins, Saccharomyces cerevisiae, Thymidine Kinase, Transcription, Genetic, Transfection, Chloramphenicol O-Acetyltransferase, Trans-Activators, Interleukin-6, Proto-Oncogene Proteins c-jun, Proto-Oncogene Proteins c-fos, Sequence Deletion, Transcription Factor AP-1, Two-Hybrid System Techniques, STAT3 Transcription Factor, Rats, Protein Multimerization
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