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.
Susini
L
L
Molecular Engines Laboratories, 20 Rue Bouvier, 75011 Paris, France.
Passer
B J
BJ
Amzallag-Elbaz
N
N
Juven-Gershon
T
T
Prieur
S
S
Privat
N
N
Tuynder
M
M
Gendron
M C
MC
Israël
A
A
Amson
R
R
Oren
M
M
Telerman
A
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D015536:Down-Regulation / Q000502:physiology; D004330:Drosophila; D029721:Drosophila Proteins; D006801:Humans; D006868:Hydrolysis; D007605:Juvenile Hormones / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D011485:Protein Binding; D051880:Receptors, Notch; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins
D029721:Drosophila Proteins; D007605:Juvenile Hormones; D008565:Membrane Proteins; C497759:N protein, Drosophila; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D051880:Receptors, Notch; D016159:Tumor Suppressor Protein p53; C060606:numb protein, Drosophila; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins