Reactome | NUMB:ITCH bind and ubiquitnate GLI1

NUMB:ITCH bind and ubiquitnate GLI1

Stable Identifier

R-HSA-5610737

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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 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
20818436	Numb activates the E3 ligase Itch to control Gli1 function through a novel degradation signal Di Marcotullio, L, Greco, A, Mazzà, D, Canettieri, G, Pietrosanti, L, Infante, P, Coni, S, Moretti, M, De Smaele, E, Ferretti, E, Screpanti, I, Gulino, A	Oncogene	2011