SCF(beta-TrCP) ubiquitinates p-GLI1

Stable Identifier
R-HSA-5610742
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

GLI1 protein is degraded by the proteasome in the absence of Hh signal. GLI1 levels are stabilized by treatment of cells with the proteasome inhibitor MG312, and GLI1 and beta-TrCP1 co-precipitate when expressed in NIH 3T3 cells.
Two SCF(beta-TrCP)-dependent degradation sites, Dn and Dc, have been identified in human GLI1. Removal of these sites abrogates the interaction with beta-TrCP, reduces the beta-TrCP-dependent ubiquitination of GLI1 and stabilizes the GLI1 protein levels. As is the case for GLI2 and GLI3, ubiquitination of GLI1 depends on the its prior phosphorylation by PKA, as GLI1 degradation is sensitive to PKA inhibitors and removal of the putative PKA sites abrogates the interaction with beta-TrCP and delays the kinetics of degradation (Huntzicker et al, 2006).

Literature References
PubMed ID Title Journal Year
16421275 Dual degradation signals control Gli protein stability and tumor formation Genes Dev. 2006
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
ubiquitin-protein transferase activity of BTRC:CUL1:RBX1:SKP1 [cytosol]
Physical Entity
Activity
Orthologous Events