Figure 10: Proposed model for Hippi/Hip-1 mediated apoptosis.

Hip-1 is normally bound and sequestered by wild-type Htt (polyglutamine (Q) < 35 residues). Expansion of the Htt polyQ stretch to > 35 residues results in lower affinity for Hip-1, freeing Hip-1 to bind to Hippi. Hippi and Hip-1 form a complex that sequesters procaspase-8 and activates it, presumably by proximity-induced autocatalytic maturation, leading to apoptosis.