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

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

Open access
Choy, Lisa, Derynck, Rik·2003·Journal of Biological Chemistry

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.

Integrity signals

Registry

Crossref · 10.1074/jbc.m212259200

Cites

65 of 65 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • TGF-β inhibits adipocyte differentiation in vitro.

    “While TGF-β inhibits adipocyte differentiation in vitro 97 and TGF-β expression in fat is paradoxically increased with obesity in rodents and humans 98,99.”

    From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [97]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Choy, L., & Derynck, R.
Affiliations
University of California, San Francisco (US)
Corresponding author
Derynck, Rik
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2003-03
Volume
278
Issue
11
Pages
9609-9619
ISSN
0021-9258 (ISSN-L)
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
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 › Epidemiology › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review