Document Detail


The intracellular domain of mouse Notch: a constitutively activated repressor of myogenesis directed at the basic helix-loop-helix region of MyoD.
MedLine Citation:
PMID:  7956819     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We show that Myf-5 and mNotch mRNA are both present in the presomitic mesoderm before muscle cell commitment and before muscle structural gene activation. The failure of presomitic mesoderm to respond to Myf-5 and express myogenic properties implies that there may be a mechanism in presomitic mesoderm to suppress muscle differentiation. Here we show that ectopic expression of the intracellular domain of mNotch (mNotchIC) functions as a constitutively activated repressor of myogenesis both in cultured cells and in frog embryos. Mutagenesis experiments indicate that the target for inactivation by mNotch is the MyoD basic helix-loop-helix domain. mNotchIC contains a nuclear localization signal and localizes to the nucleus. Removal of the nuclear localization signal (NLS) reduces nuclear localization and diminishes the inhibition of myogenesis caused by Myf-5 or MyoD. Additional experiments show that the CDC10/SWI6/ankyrin repeats are also necessary for myogenic inhibition.
Authors:
R Kopan; J S Nye; H Weintraub
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  120     ISSN:  0950-1991     ISO Abbreviation:  Development     Publication Date:  1994 Sep 
Date Detail:
Created Date:  1994-12-23     Completed Date:  1994-12-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  2385-96     Citation Subset:  IM    
Affiliation:
Fred Hutchinson Cancer Research Center, Howard Hughes Medical Institute, Seattle, WA 98104.
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Cloning, Molecular
DNA-Binding Proteins*
Gene Expression
Helix-Loop-Helix Motifs*
In Situ Hybridization
Membrane Proteins / genetics*
Mice
Mice, Inbred Strains
Molecular Sequence Data
Morphogenesis / genetics
Muscle Proteins / genetics
Muscles / embryology*
MyoD Protein / genetics*
Myogenic Regulatory Factor 5
Polymerase Chain Reaction
Receptor, Notch1
Receptors, Cell Surface*
Repressor Proteins / genetics*
Trans-Activators*
Transcription Factors / genetics
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Membrane Proteins; 0/Muscle Proteins; 0/Myf5 protein, mouse; 0/MyoD Protein; 0/MyoD1 myogenic differentiation protein; 0/Myogenic Regulatory Factor 5; 0/Notch1 protein, mouse; 0/Receptor, Notch1; 0/Receptors, Cell Surface; 0/Repressor Proteins; 0/Trans-Activators; 0/Transcription Factors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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