Fig. 8
From: ERAP1 promotes Hedgehog-dependent tumorigenesis by controlling USP47-mediated degradation of βTrCP
A representative model showing the role of ERAP1 in Hh-dependent tumorigenesis. ERAP1 promotes ubiquitylation and proteasomal degradation of βTrCP by sequestering USP47. This event leads to increase of Gli1 and Gli2 protein levels and decrease of Gli3R, thus triggering the Hh pathway and favoring cell growth and tumorigenesis. In the absence of ERAP1, USP47 binds and stabilizes βTrCP, which, in turn, promotes ubiquitylation and proteasomal degradation of Gli1 and Gli2, and ubiquitylation and proteolytic cleavage of Gli3 into the repressor form Gli3R. These events lead to the repression of the Hh pathway and inhibition of cell proliferation and tumor growth
