Evidence map›Paper›PMID 15340086›Full record

ArticleMolecular and cellular biology2004

Phosphorylation and alternative pre-mRNA splicing converge to regulate myocyte enhancer factor 2C activity.

Bangmin Zhu, Tod Gulick

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

48 citing papers in PubMed, 86 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Sleep need driven oscillation of glutamate synaptic phenotype.bioRxiv : the preprint server for biology · 2024
    Article
  5. Article
  6. Posttranscriptional Regulation by Proteins and Noncoding RNAs.Advances in experimental medicine and biology · 2024
    Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Genes of the cGMP-PKG-CaBiochimica et biophysica acta. Molecular basis of disease · 2020
    Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Review
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

2 authors at 1 institution in 1 country.

Bangmin ZhuDiabetes Research Laboratory, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Tod Gulick
Harvard University · US

Funding

Mitochondrial Nucleotide Carriers of NRTI MetabolitesR01HL072713 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI GULICK, TOD · 2003 to 2007
$1.9M
CARNITINE PALMITOYLTRANSFERASE I ISOFORM FUNCTIONR01DK055875 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI GULICK, TOD · 2001 to 2005
$1.5M
MITOCHONDRIAL OXIDATIVE ENZYME EXPRESSIONK02DK002461 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI GULICK, TOD · 1996 to 2000
$103k
NHLBI NIH HHS HL72713NHLBI NIH HHS R01 HL072713NIDDK NIH HHS DK02461NIDDK NIH HHS DK55875NIDDK NIH HHS R01 DK055875
6 · The paper itself

Abstract

Myocyte enhancer factor 2 (MEF2) transcription factors play pivotal roles in cardiac, muscle, and neuron gene expression. All products of MEF2 genes have a common amino-terminal DNA binding and dimerization domain, but the four vertebrate MEF2 gene transcripts are alternatively spliced among coding exons to produce splicing isoforms. In MEF2C alone, alternative splice acceptors in the last exon give forms that include or exclude a short domain that we designate gamma. We show that MEF2C is expressed exclusively as gamma- isoforms in heart tissue and predominantly as gamma- in other adult tissues and in differentiating myocytes. MEF2C gamma- isoforms are much more robust than gamma+ forms in activating MEF2-responsive reporters in transfected fibroblasts despite indistinguishable expression levels, and they better synergize with MyoD in promoting myogenic conversion. One-hybrid transcription assays using Gal4-MEF2C fusions give similar distinctions between gamma- and gamma+ isoforms in all cell types tested, including myocytes. Cis effects of gamma on MEF2C DNA binding, dimerization, protein stability, or response to CaM or p38 mitogen-activated protein kinase signaling are not apparent, and the isolated gamma domain represses transcription when fused to Gal4. One phosphoserine residue is present within the gamma domain according to tandem mass spectrometry, and mutation of this residue abolishes gamma-mediated transrepression. A similar activity is present in the constitutive gamma domain and serine phosphoacceptor of MEF2A. Our findings indicate that gamma functions autonomously as a phosphoserine-dependent transrepressor to downregulate transactivation function of MEF2 factors and that alternative splicing and serine phosphorylation converge to provide complex combinatorial control of MEF2C activity.

Indexed as

Alternative SplicingAmino Acid SequenceAnimalsBase SequenceCell LineCOS CellsDNAHeLa CellsHumansMADS Domain ProteinsMAP Kinase Signaling SystemMEF2 Transcription FactorsMiceMolecular Sequence DataMuscle DevelopmentMyogenic Regulatory FactorsDNAMADS Domain ProteinsMEF2C protein, humanMef2c protein, mouseMEF2 Transcription FactorsMyogenic Regulatory FactorsProtein IsoformsRecombinant Fusion ProteinsRNA PrecursorsSerine

Identifiers

PMID15340086
PMCPMC515034
OpenAlexW2096720891

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.