Signalling downstream of activated mammalian Notch.
Notch belongs to a family of transmembrane proteins that are widely conserved from flies to vertebrates and are thought to be involved in cell-fate decisions. In Drosophila, the Suppressor of hairless (Su(H)) gene and genes of the Enhancer of split (E(Spl)) complex, which encode proteins of the basic helix-loop-helix type have been implicated in the Notch signalling pathway. Mammalian homologues of E(Spl), such as the mouse Hairy enhancer of split (HES-1), have been isolated. Both HES-1 and the intracellular domain of murine Notch (mNotch) are able to block MyoD-induced myogenesis. Here we show that activated forms of mNotch associate with the human analogue of Su(H), KBF2/RBP-J kappa (refs 8,9) and act as transcriptional activators through the KBF2-binding sites of the HES-1 promoter.
Jarriault
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S
Unité de Biologie Moléculaire de L'Expression Génique, URA 1149 CNRS, Institut Pasteur, Paris, France.
Brou
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C
Logeat
F
F
Schroeter
E H
EH
Kopan
R
R
Israel
A
A
D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D051880:Receptors, Notch; D012097:Repressor Proteins / Q000235:genetics; D000072056:Transcription Factor HES-1; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D008565:Membrane Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D051880:Receptors, Notch; D012097:Repressor Proteins; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; C489734:Hes1 protein, mouse; C497759:N protein, Drosophila; C497570:RBPJ protein, human; C497571:Rbpj protein, mouse; C088731:Su(H) protein, Drosophila; C078493:HES1 protein, human