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    Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15067-72.

    Siah-1 binds and regulates the function of Numb.

    Susini L, Passer BJ, Amzallag-Elbaz N, Juven-Gershon T, Prieur S, Privat N, Tuynder M, Gendron MC, Israël A, Amson R, Oren M, Telerman A.

    Molecular Engines Laboratories, 20 Rue Bouvier, 75011 Paris, France.

    The Drosophila Seven in absentia (Sina) gene product originally was described as a protein that controls cell fate decisions during eye development. Its mammalian homolog, Siah-1, recently was found to be involved in p53-dependent and -independent pathways of apoptosis and G(1) arrest. We report that Siah-1 interacts directly with and promotes the degradation of the cell fate regulator Numb. Siah-1-mediated Numb degradation leads to redistribution of endogenous cell-surface Notch to the cytoplasm and nucleus and to augmented Notch-regulated transcriptional activity. These data imply that through its ability to target Numb for degradation, Siah-1 can act as a key regulator of Numb-related activities, including Notch signaling.

    PMID: 11752454 [PubMed - indexed for MEDLINE]

    PMCID: PMC64984

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