RGD Reference Report - Muscle LIM protein promotes myogenesis by enhancing the activity of MyoD. - Rat Genome Database

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Muscle LIM protein promotes myogenesis by enhancing the activity of MyoD.

Authors: Kong, Y  Flick, MJ  Kudla, AJ  Konieczny, SF 
Citation: Kong Y, etal., Mol Cell Biol. 1997 Aug;17(8):4750-60.
RGD ID: 10047266
Pubmed: PMID:9234731   (View Abstract at PubMed)
PMCID: PMC232327   (View Article at PubMed Central)

The muscle LIM protein (MLP) is a muscle-specific LIM-only factor that exhibits a dual subcellular localization, being present in both the nucleus and in the cytoplasm. Overexpression of MLP in C2C12 myoblasts enhances skeletal myogenesis, whereas inhibition of MLP activity blocks terminal differentiation. Thus, MLP functions as a positive developmental regulator, although the mechanism through which MLP promotes terminal differentiation events remains unknown. While examining the distinct roles associated with the nuclear and cytoplasmic forms of MLP, we found that nuclear MLP functions through a physical interaction with the muscle basic helix-loop-helix (bHLH) transcription factors MyoD, MRF4, and myogenin. This interaction is highly specific since MLP does not associate with nonmuscle bHLH proteins E12 or E47 or with the myocyte enhancer factor-2 (MEF2) protein, which acts cooperatively with the myogenic bHLH proteins to promote myogenesis. The first LIM motif in MLP and the highly conserved bHLH region of MyoD are responsible for mediating the association between these muscle-specific factors. MLP also interacts with MyoD-E47 heterodimers, leading to an increase in the DNA-binding activity associated with this active bHLH complex. Although MLP lacks a functional transcription activation domain, we propose that it serves as a cofactor for the myogenic bHLH proteins by increasing their interaction with specific DNA regulatory elements. Thus, the functional complex of MLP-MyoD-E protein reveals a novel mechanism for both initiating and maintaining the myogenic program and suggests a global strategy for how LIM-only proteins may control a variety of developmental pathways.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of myotube differentiation acts_upstream_of_or_withinIGIUniProtKB:P1008510047266PMID:9234731MGI 
positive regulation of myotube differentiation acts_upstream_of_or_withinIDA 10047266PMID:9234731MGI 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cytoplasm located_inIDA 10047266PMID:9234731MGI 
nucleus located_inIDA 10047266PMID:9234731MGI 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Csrp3  (cysteine and glycine rich protein 3)


Additional Information