Siah-1 binds and regulates the function of Numb.
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.
Mesh Terms:
Animals, Apoptosis, Cell Line, Down-Regulation, Drosophila, Drosophila Proteins, Humans, Hydrolysis, Juvenile Hormones, Membrane Proteins, Nuclear Proteins, Oligonucleotides, Antisense, Protein Binding, Receptors, Notch, Tumor Suppressor Protein p53, Two-Hybrid System Techniques, Ubiquitin-Protein Ligases
Animals, Apoptosis, Cell Line, Down-Regulation, Drosophila, Drosophila Proteins, Humans, Hydrolysis, Juvenile Hormones, Membrane Proteins, Nuclear Proteins, Oligonucleotides, Antisense, Protein Binding, Receptors, Notch, Tumor Suppressor Protein p53, Two-Hybrid System Techniques, Ubiquitin-Protein Ligases
Proc. Natl. Acad. Sci. U.S.A.
Date: Dec. 18, 2001
PubMed ID: 11752454
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