The DOI matches its Crossref record; 77 of the 80 references it cites were found in a registry or an index.
TGF-β inhibits muscle differentiation through functional repression of myogenic transcription factors by Smad3
Open accessAbstract
Transforming growth factor-β (TGF-β) is a potent inhibitor of skeletal muscle differentiation, but the molecular mechanism and signaling events that lead to this inhibition are poorly characterized. Here we show that the TGF-β intracellular effector Smad3, but not Smad2, mediates the inhibition of myogenic differentiation in MyoD-expressing C3H10T1/2 cells and C2C12 myoblasts by repressing the activity of the MyoD family of transcriptional factors. The Smad3-mediated repression was directed at the E-box sequence motif within muscle gene enhancers and the bHLH region of MyoD, the domain required for its association with E-protein partners such as E12 and E47. The repression could be overcome by supplying an excess of E12, and covalent tethering of E47 to MyoD rendered the E-box-dependent transcriptional activity refractory to the effects of Smad3 and TGF-β. Smad3 physically interacted with the HLH domain of MyoD, and this interaction correlated with the ability of Smad3 to interfere with MyoD/E protein heterodimerization and binding of MyoD complexes to oligomerized E-box sites. Together, these results reveal a model for how TGF-β, through Smad3-mediated transcriptional repression, inhibits myogenic differentiation.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Myostatin is a ligand of the TGF-β pathway in skeletal muscle and a well-known negative regulator of muscle mass, as it inhibits satellite cells’ proliferation and differentiation [174].”
From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [174]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Expression of a single transfected cDNA converts fibroblasts to myoblasts
Davis, R. L., Weintraub, H. M., & Lassar, A. B. (1987) · Cell · doi:10.1016/0092-8674(87)90585-x · Cited by 3,388
Murre, C., Page-McCaw, P., & Baltimore, D. (1989) · Cell · doi:10.1016/0092-8674(89)90682-x · Cited by 2,713
The protein Id: A negative regulator of helix-loop-helix DNA binding proteins
Benezra, R., Davis, R. L., Lockshon, D., Turner, D. L., & Weintraub, H. M. (1990) · Cell · doi:10.1016/0092-8674(90)90214-y · Cited by 2,202
Transcriptional control by the TGF‐β/Smad signaling system
Massagué, J., & Wotton, D. (2000) · The EMBO Journal · doi:10.1093/emboj/19.8.1745 · Cited by 1,990
The MyoD family and myogenesis: Redundancy, networks, and thresholds
Weintraub, H. (1993) · Cell · doi:10.1016/0092-8674(93)90610-3 · Cited by 1,057
TRANSCRIPTIONAL CONTROL OF MUSCLE DEVELOPMENT BY MYOCYTE ENHANCER FACTOR-2 (MEF2) PROTEINS
Black, B. L., & Olson, E. N. (1998) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.14.1.167 · Cited by 1,037
Self-citationTranscriptional Activators of TGF-β Responses: Smads
Derynck, R., Zhang, Y. E., & Feng, X. (1998) · Cell · doi:10.1016/s0092-8674(00)81696-7 · Cited by 1,030
Self-citationBraun, T. W., Buschhausen-Denker, G., Bober, E., Tannich, E., & Arnold, H.-H. (1989) · The EMBO Journal · doi:10.1002/j.1460-2075.1989.tb03429.x · Cited by 906
Receptor-associated Mad homologues synergize as effectors of the TGF-β response
Zhang, Y. E., Feng, X., Wu, R.-Y., & Derynck, R. (1996) · Nature · doi:10.1038/383168a0 · Cited by 873
Self-citationLassar, A. B., Davis, R. L., Wright, W. E., Kadesch, T. R., Murre, C., Voronova, A., Baltimore, D., & Weintraub, H. M. (1991) · Cell · doi:10.1016/0092-8674(91)90620-e · Cited by 836
Flagged first, then by citations
3 of the 80 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- 10.1210/me.13.7.1155 · DOI
Cited by
Sorted by citations
Items 401–402 of 402
Song, Y., Guo, X., Zhang, X., Zhang, J., Sheng, H., & Chu, M. (2026) · Veterinary Quarterly · doi:10.1080/01652176.2026.2720646
Engelbrecht, L. (2013) · SUNScholar (Stellenbosch University)
Metadata
- Authors
- Liu, D., Black, B. L., & Derynck, R.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2001-11-15
- Volume
- 15
- Issue
- 22
- Pages
- 2950-2966
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC312830
- OpenAlex
- W2116961946
- Cited by
- 399
- References
- 80
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 22 · 2023: 16 · 2022: 23 · 2021: 16 · 2020: 11 · 2019: 26 · 2018: 19 · 2017: 13 · 2016: 19 · 2015: 13 · 2014: 9 · 2013: 27 · 2012: 14
- Type
- posted content
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA063101, R01-CA63101)
- 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 › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- TGF-beta, Smad3, Smad2, skeletal muscle differentiation, myogenesis, MyoD, E-box, bHLH transcription factors, E12, E47, E protein, transcriptional repression, heterodimerization, C2C12 myoblasts, C3H10T1/2 cells
- MeSH terms
- Animals, Cell Differentiation, Cell Line, Cells, Cultured, DNA-Binding Proteins, Glutathione Transferase, Luciferases, Microscopy, Fluorescence, Plasmids, Protein Binding, Recombinant Fusion Proteins, Retroviridae, Transcription, Genetic, Transfection, Blotting, Western, Signal Transduction, Trans-Activators, Transforming Growth Factor beta, Protein Structure, Tertiary, MyoD Protein, Muscle, Skeletal, Dimerization, COS Cells, Mice, Smad3 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
