NUMB binds ITCH

Stable Identifier
R-HSA-5610735
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

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
20818436 Numb activates the E3 ligase Itch to control Gli1 function through a novel degradation signal

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

Oncogene 2011
17115028 Numb is a suppressor of Hedgehog signalling and targets Gli1 for Itch-dependent ubiquitination

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

Nat. Cell Biol. 2006
Participants
Participant Of
Orthologous Events
Authored
Reviewed