NUMB binds ITCH

Stable Identifier
R-HSA-5610735
Type
Reaction [binding]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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NUMB is a negative regulator of Hh signaling that acts by promoting the ITCH-dependent ubiquitination of GLI1. ITCH is an E3 ligase that is kept in an inactive conformation by an intramolecular interaction between the HECT domain and a WW motif. Binding of the adaptor protein NUMB to the WW region of ITCH displaces the HECT domain and promotes the catalytic activity of the E3 ligase (di Marcotullio et al, 2006; 2011).
Literature References
PubMed ID Title Journal Year
17115028 Numb is a suppressor of Hedgehog signalling and targets Gli1 for Itch-dependent ubiquitination

De Smaele, E, Gulino, A, Sico, MA, Screpanti, I, Ferretti, E, Maroder, M, Alimandi, M, Di Marcotullio, L, Giannini, G, Po, A, Greco, A

Nat. Cell Biol. 2006
20818436 Numb activates the E3 ligase Itch to control Gli1 function through a novel degradation signal

Canettieri, G, Pietrosanti, L, MazzĂ , D, Screpanti, I, Greco, A, Coni, S, Gulino, A, De Smaele, E, Di Marcotullio, L, Infante, P, Ferretti, E, Moretti, M

Oncogene 2011
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