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Cited by 343TGF-β signaling in diseasesPeroxisome Proliferator-Activated ReceptorsAdipokines, Inflammation, and Metabolic Diseases

The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.

Transforming Growth Factor-β Inhibits Adipocyte Differentiation by Smad3 Interacting with CCAAT/Enhancer-binding Protein (C/EBP) and Repressing C/EBP Transactivation Function

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Choy, Lisa, Derynck, Rik·2003·Journal of Biological Chemistry
DOI 10.1074/jbc.m212259200
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Abstract

Transforming growth factor (TGF)-beta is a potent inhibitor of adipocyte differentiation. To identify which adipocyte transcription factors might be targeted by TGF-beta, we overexpressed key adipogenic transcription factors, C/EBPbeta, C/EBPdelta, or peroxisome proliferator-activated receptor (PPAR) gamma in NIH3T3 cells and tested the ability of TGF-beta to block adipogenesis. We show that TGF-beta inhibits adipocyte differentiation driven by either C/EBPbeta or C/EBPdelta without affecting C/EBP protein expression levels, suggesting that these C/EBPs are a direct target of TGF-beta action. Because TGF-beta inhibits adipogenesis by signaling through Smad3, we examined physical and functional interactions of Smad3 and Smad4 with C/EBPbeta, C/EBPdelta, and PPARgamma2. C/EBPbeta and C/EBPdelta were found to physically interact with Smad3 and Smad4, and Smad3 cooperated with Smad4 and TGF-beta signaling to repress the transcriptional activity of C/EBPs. Thus, repression of the activity of C/EBPs by Smad3/4 at C/EBP binding sites inhibited transcription from the PPARgamma2 and leptin promoters. In contrast, PPARgamma interacted only very weakly with Smad3 and its transcriptional activity was not repressed by Smad3/4 or in response to TGF-beta. Smad3/4 did not reduce the ability of C/EBP to bind to its cognate DNA sequence, but repressed transcription by inhibiting the transactivation function of C/EBP.

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Research works printed but not linked: 5

  1. Saladin, 1999, Cell Growth Differ., 10, 43
  2. Centrella, 1994, Endocr. Rev., 15, 27
  3. Sparks, 1993, Cancer Res., 53, 1770
  4. Herrera, 1989, Mol. Cell. Biol., 9, 5331
  5. Hayes, 2001, Cancer Res., 61, 2112

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Metadata

Authors
Choy, L., & Derynck, R.
Affiliations
University of California, San Francisco (US)
Corresponding author
Derynck, Rik
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2003-03
Volume
278
Issue
11
Pages
9609-9619
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m212259200
OpenAlex
W2017292651
Cited by
343
References
64
Citations by year
2026: 5 · 2025: 13 · 2024: 9 · 2023: 14 · 2022: 13 · 2021: 19 · 2020: 19 · 2019: 18 · 2018: 21 · 2017: 21 · 2016: 13 · 2015: 21 · 2014: 10 · 2013: 27 · 2012: 21
FWCI
3.68
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (1k01dk002877-01)
  • National Cancer Institute (R01CA063101, R01-CA63101)
  • National Institute of Diabetes and Digestive and Kidney Diseases (K01 DK02877)
  • National Institute of Dental and Craniofacial Research (P60DE013058, P60 DE-13058)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords
TGF-beta, adipogenesis, Smad3, SMAD4, C/EBPβ, C/EBPδ, PPARγ, transcriptional repression, protein-protein interaction, TGF-beta signaling
MeSH terms
Animals, Binding Sites, Cell Differentiation, Cell Line, DNA-Binding Proteins, Glutathione Transferase, Oligonucleotides, Plasmids, Precipitin Tests, Promoter Regions, Genetic, Protein Binding, RNA, Transcription Factors, Transcription, Genetic, Transfection, Transcriptional Activation, Trans-Activators, Transforming Growth Factor beta, 3T3 Cells, Protein Structure, Tertiary, Adipocytes, Receptors, Cytoplasmic and Nuclear, Biotinylation, Leptin, CCAAT-Enhancer-Binding Proteins, CCAAT-Enhancer-Binding Protein-beta, Lipid Metabolism, Mice, CCAAT-Enhancer-Binding Protein-delta, Smad3 Protein, Smad4 Protein

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