Fig. 2. Type I noncanonical Hh signaling.

In the absence of a Hh ligand (left) Ptc interacts with cyclin B1 and a proapoptotic complex that includes caspase-9, the CARD (caspase-associated recruitment domain)-domain containing protein Tucan-1, and the adaptor protein Dral. The interaction with cyclin B1 inhibits proliferation by sequestering cyclin B1 outside the nucleus. In some cell types, Ptc recruitment of this proapoptotic complex depends on a preceding cleavage event in the C-terminal domain of Ptc by caspase-3 and results in nucleation and activation of caspase-9. Active caspase-9 speeds the formation of this complex by promoting activation of caspase-3, leading to apoptosis. Hh binding (right) disrupts the interaction of Ptc with cyclin B1 and the proapoptotic complex, likely through a conformational change in Ptc, leading to increased proliferation and survival. Yellow highlighted and shaded caspase shapes indicate active and inactive caspases, respectively.