Matches in SemOpenAlex for { <https://semopenalex.org/work/W65532905> ?p ?o ?g. }
- W65532905 abstract "The Notch signaling pathway is essential in many cell fate decisions in invertebrates as well as in vertebrates. After ligand binding, a two-step proteolytic cleavage releases the intracellular part of the receptor, which translocates to the nucleus and acts as a transcriptional activator. Though Notch-induced transcription of genes has been extensively reported, its endogenous nuclear form has seldom been visualized. We report that the nuclear intracellular domain of Notch 1 is stabilized by proteasome inhibitors, suggesting an involvement of the ubiquitin-proteasome pathway. SEL-10, an F-box protein of the Cdc4 family, was isolated in a genetic screen for Linl2/Notch negative regulators in Caenorhabditis elegans. We isolated human and murine counterparts of SEL-10 and investigated the role of a dominant-negative form of this protein, deleted of the F-box, on Notch 1 stability and activity. This molecule could stabilize intracellular Notch 1 and enhance its transcriptional activity, but had no effect on inactive, membrane-anchored forms of the receptor. We then demonstrated that SEL-10 specifically interacts with nuclear forms of Notchl and that this interaction requires a phosphorylation event. Taken together, these data suggest that SEL-10 is involved in shutting-off Notch signaling by ubiquitin-proteasome-mediated degradation of the active transcriptional factor, following a nuclear phosphorylation event." @default.
- W65532905 created "2016-06-24" @default.
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- W65532905 date "2002-01-01" @default.
- W65532905 modified "2023-09-23" @default.
- W65532905 title "Control of Notch Activity by the Ubiquitin-Proteasome Pathway" @default.
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- W65532905 doi "https://doi.org/10.1007/978-3-642-55996-9_3" @default.
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