Evidence map›Paper›PMID 21964591›Full record

ArticleMolecular endocrinology (Baltimore, Md.)2011

Myostatin induces degradation of sarcomeric proteins through a Smad3 signaling mechanism during skeletal muscle wasting.

Sudarsanareddy Lokireddy, Craig McFarlane, Xiaojia Ge, Huoming Zhang, Siu Kwan Sze, Mridula Sharma, Ravi Kambadur

RetractedErratum issuedOpen access · bronzeAbstract readRetracted Publication
In one paragraph

Article in Molecular endocrinology (Baltimore, Md.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
6.9field-weighted citation impact, top 2% 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

57 citing papers in PubMed, 116 citations in OpenAlex.

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  5. Feasibility ofDiagnostics (Basel, Switzerland) · 2022
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  13. Short-term creatine supplementation changes protein metabolism signaling in hindlimb suspension.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2019
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  18. Myostatin promotes distinct responses on protein metabolism of skeletal and cardiac muscle fibers of rodents.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2017
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Sudarsanareddy LokireddySchool of Biological Sciences, Nanyang Technological University, Singapore.
Craig McFarlane
Xiaojia Ge
Huoming Zhang
Siu Kwan Sze
Mridula Sharma
Ravi Kambadur
Nanyang Technological University · SGAgency for Science, Technology and Research · SGNational University of Singapore · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ubiquitination-mediated proteolysis is a hallmark of skeletal muscle wasting manifested in response to negative growth factors, including myostatin. Thus, the characterization of signaling mechanisms that induce the ubiquitination of intracellular and sarcomeric proteins during skeletal muscle wasting is of great importance. We have recently characterized myostatin as a potent negative regulator of myogenesis and further demonstrated that elevated levels of myostatin in circulation results in the up-regulation of the muscle-specific E3 ligases, Atrogin-1 and muscle ring finger protein 1 (MuRF1). However, the exact signaling mechanisms by which myostatin regulates the expression of Atrogin-1 and MuRF1, as well as the proteins targeted for degradation in response to excess myostatin, remain to be elucidated. In this report, we have demonstrated that myostatin signals through Smad3 (mothers against decapentaplegic homolog 3) to activate forkhead box O1 and Atrogin-1 expression, which further promotes the ubiquitination and subsequent proteasome-mediated degradation of critical sarcomeric proteins. Smad3 signaling was dispensable for myostatin-dependent overexpression of MuRF1. Although down-regulation of Atrogin-1 expression rescued approximately 80% of sarcomeric protein loss induced by myostatin, only about 20% rescue was seen when MuRF1 was silenced, implicating that Atrogin-1 is the predominant E3 ligase through which myostatin manifests skeletal muscle wasting. Furthermore, we have highlighted that Atrogin-1 not only associates with myosin heavy and light chain, but it also ubiquitinates these sarcomeric proteins. Based on presented data we propose a model whereby myostatin induces skeletal muscle wasting through targeting sarcomeric proteins via Smad3-mediated up-regulation of Atrogin-1 and forkhead box O1.

Indexed as

Activin Receptors, Type IIAnimalsCell LineCells, CulturedFollistatinForkhead Box Protein O1Forkhead Transcription FactorsImmunoblottingImmunoprecipitationMiceMice, Inbred C57BLMice, Mutant StrainsMuscle Fibers, SkeletalMuscle ProteinsMuscle, SkeletalMyostatinActivin Receptors, Type IIactivin receptor type II-BFbxo32 protein, mouseFollistatinForkhead Box Protein O1Forkhead Transcription FactorsFoxo1 protein, mouseMuscle ProteinsMyostatinSKP Cullin F-Box Protein LigasesSmad3 ProteinTrim63 protein, mouseTripartite Motif ProteinsUbiquitin-Protein Ligases

Identifiers

PMID21964591
PMCPMC5417176
OpenAlexW2138904483

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.