Figure 4.

Role of Itch in Type I non-canonical Hh pathway. (A) In the absence of Hh, PTCH1 recruits a pro-apoptotic complex, including DRAL, TUCAN1 and Caspase 9, to its C-Terminal Domain (CTD). The activation of the Caspase 9 promotes the cleavage of the PTCH1 CTD by the Caspase 3, leading to irreversible commitment to cell death. (B) In the presence of Itch, the Lys1413 at the PTCH1 CTD is ubiquitylated, leading to the internalization and degradation of the PTCH1 and to the impairment of its pro-apoptotic activity.