NUMB:ITCH binds GLI1

Stable Identifier
R-HSA-5635861
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

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).

Literature References
PubMed ID Title Journal Year
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
16421275 Dual degradation signals control Gli protein stability and tumor formation

Huntzicker, EG, Estay, IS, Zhen, H, Lokteva, LA, Jackson, PK, Oro, AE

Genes Dev. 2006
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
Participants
Participant Of
Orthologous Events
Authored
Reviewed