NUMB:ITCH binds GLI1

Stable Identifier
R-HSA-5635861
Type
Reaction [binding]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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SVG |   | PPTX  | SBGN
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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).
Literature References
PubMed ID Title Journal Year
16421275 Dual degradation signals control Gli protein stability and tumor formation

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

Genes Dev. 2006
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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