Abstract
Notch controls cell fate by inhibiting cellular differentiation, presumably through activation of the transcriptional regulator human C promoter Binding Factor (CBF1), which transactivates the hairy and Enhancer of split (HES-1) gene. However, we describe constitutively active forms of Notch1, which inhibit muscle cell differentiation but do not interact with CBF1 or upregulate endogenous HES-1 expression. In addition, Jagged-Notch interactions that prevent the expression of muscle cell specific genes do not involve the upregulation of endogenous HES-1. In fact, exogenous expression of HES-1 in C2C12 myoblasts does not block myogenesis. Our data demonstrate the existence of a CBF1-independent pathway by which Notch inhibits differentiation. We therefore propose that Notch signaling activates at least two different pathways: one which involves CBF1 as an intermediate and one which does not.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Basic Helix-Loop-Helix Transcription Factors
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Cell Differentiation
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Cell Fusion
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Cells, Cultured
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Cytoplasm / metabolism
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DNA-Binding Proteins / metabolism
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Fungal Proteins / metabolism
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Gene Expression Regulation, Developmental*
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Homeodomain Proteins / biosynthesis
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Humans
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Molecular Sequence Data
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Muscle Development*
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Muscles / cytology
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Protein Binding
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Receptors, Notch
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Recombinant Proteins / metabolism
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Repressor Proteins
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Saccharomyces cerevisiae Proteins*
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Sequence Deletion
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Signal Transduction*
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Stem Cells / cytology
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Transcription Factor HES-1
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Up-Regulation
Substances
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Basic Helix-Loop-Helix Transcription Factors
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CBF1 protein, S cerevisiae
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DNA-Binding Proteins
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Fungal Proteins
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Hes1 protein, mouse
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Homeodomain Proteins
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Membrane Proteins
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Receptors, Notch
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Recombinant Proteins
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Repressor Proteins
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Saccharomyces cerevisiae Proteins
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Transcription Factor HES-1
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HES1 protein, human