Siah-1 binds and regulates the function of Numb
Open Access
- 18 December 2001
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 98 (26) , 15067-15072
- https://doi.org/10.1073/pnas.261571998
Abstract
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 G1 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.Keywords
This publication has 45 references indexed in Scilit:
- Aspartate Mutations in Presenilin and γ‐Secretase Inhibitors Both Impair Notch1 Proteolysis and Nuclear Translocation with Relative Preservation of Notch1 SignalingJournal of Neurochemistry, 2000
- Interaction of Alzheimer's Presenilin-1 and Presenilin-2 with Bcl-XLJournal of Biological Chemistry, 1999
- Notch Signaling: Cell Fate Control and Signal Integration in DevelopmentScience, 1999
- Mammalian homologs of seven in absentia regulate DCC via the ubiquitin–proteasome pathwayGenes & Development, 1997
- Mdm2 promotes the rapid degradation of p53Nature, 1997
- Control of Daughter Cell Fates during Asymmetric Division: Interaction of Numb and NotchNeuron, 1996
- Involvement of Notch-1 in mammalian retinal neurogenesis: association of Notch-1 activity with both immature and terminally differentiated cellsMechanisms of Development, 1995
- Signalling downstream of activated mammalian NotchNature, 1995
- Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6Nature, 1991
- seven in absentia, a gene required for specification of R7 cell fate in the Drosophila eyeCell, 1990