NUMB:ITCH bind and ubiquitnate GLI1

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
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GLI1 is recruited to the NUMB:ITCH complex through a direct interaction with both proteins. Once recruited, GLI1 is ubiquitinated by ITCH and subsequently degraded by the proteasome. ITCH-mediated degradation of GLI1 does not depend on the Dc or Dn degrons required for interaction with beta-TrCP, but instead relies on a novel PPXYs/pSP degron of GLI1 (di Marcotullio et al, 2006, 2011; Huntzicker et al, 2006). How these two apparently parallel systems of GLI1 ubiquitination and degradation are coordinated is not yet clear.
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
Catalyst Activity

ubiquitin protein ligase activity of NUMB:ITCH [cytosol]

Orthologous Events
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