Evidence map›Paper›PMID 15044954›Full record

ArticleThe EMBO journal2004

TGF-beta-activated Smad3 represses MEF2-dependent transcription in myogenic differentiation.

Dong Liu, Jong Seok Kang, Rik Derynck

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
3.6field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

63 citing papers in PubMed, 140 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Effect of Pinoresinol and Vanillic Acid Isolated fromMolecules (Basel, Switzerland) · 2022
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. EMBO reports · 2019
    Article
  16. Review
  17. Article
  18. TGF-β Family Signaling in Mesenchymal Differentiation.Cold Spring Harbor perspectives in biology · 2018
    Review
  19. Review
  20. The Discovery and Early Days of TGF-β: A Historical Perspective.Cold Spring Harbor perspectives in biology · 2016
    Review

3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Dong LiuDepartments of Growth and Development and Anatomy, Programs in Cell Biology and Developmental Biology, University of California, San Francisco, CA, USA.
Jong Seok Kang
Rik Derynck
University of California, San Francisco · US

Funding

TRANSGENIC MODELS WITH SKELETAL REPAIR PHENOTYPESP60DE013058 · NIDCR · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI DAMSKY, CAROLINE H · 1999 to 2003
$9.1M
TGF-Beta and Smad-mediated regulation of gene expressionR01CA063101 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DERYNCK, RIK M · 1995 to 2014
$6.4M
NCI NIH HHS R01 CA063101NCI NIH HHS R01-CA63101NIDCR NIH HHS P60 DE013058NIDCR NIH HHS P60 DE-13058
6 · The paper itself

Abstract

Transforming growth factor beta (TGF-beta) inhibits myogenesis and associated gene expression. We previously reported that the TGF-beta signaling effector Smad3 mediates this inhibition, by interfering with the assembly of myogenic bHLH transcription factor heterodimers on E-box sequences in the regulatory regions of muscle-specific genes. We now show that TGF-beta-activated Smad3 suppresses the function of MEF2, a second class of essential myogenic factors. TGF-beta signaling through Smad3 represses myogenin expression independently of E-boxes, and prevents a tethered MyoD-E47 dimer to activate transcription indirectly through MEF2-binding sites. In addition, Smad3 interacts with MEF2C, which requires its MADS domain, and disrupts its association with the SRC-family coactivator GRIP-1, thus diminishing the transcription activity of MEF2C. Consistent with this physical displacement, TGF-beta signaling blocks the GRIP-1-induced redistribution of MEF2C to discrete nuclear subdomains in 10T1/2 cells, and the recruitment of GRIP-1 to the myogenin promoter in differentiating myoblasts. These findings indicate that the TGF-beta/Smad3 pathway targets two critical components of the myogenic transcription machinery to inhibit terminal differentiation.

Indexed as

Transcription, GeneticAnimalsCell DifferentiationCell LineCell NucleusDNA-Binding ProteinsGene Expression RegulationGenes, ReporterMEF2 Transcription FactorsMuscle CellsMyogenic Regulatory FactorsNuclear Receptor Coactivator 2Promoter Regions, GeneticProtein BindingProtein Structure, TertiaryRecombinant Fusion ProteinsDNA-Binding ProteinsMEF2 Transcription FactorsMyogenic Regulatory FactorsNuclear Receptor Coactivator 2Recombinant Fusion ProteinsSmad3 ProteinTrans-ActivatorsTranscription FactorsTransforming Growth Factor beta

Identifiers

PMID15044954
PMCPMC391082
OpenAlexW2171308503

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.