Fig. 5.

Sufu and HIB/SPOP action on Ci/Gli proteins. A model of how Sufu protects Ci/Gli proteins from HIB/SPOP-promoted degradation. (A) Fly Su(fu) binds Ci-155 and competitively inhibits HIB binding, which recruits the Cul3 E3 ligase and completely degrades Ci. Depending on the state of Hh pathway activation, Ci is either processed into the Ci-75 repressor after dissociation from Su(fu) or activates transcription of Hh target genes such as Ptc and HIB. Su(fu) also impedes nuclear accumulation of Ci-155. (B) Mouse Sufu binds to Gli2 and Gli3, protecting them from SPOP-mediated degradation. As in Drosophila, Gli2 and Gli3 are either proteolytically processed into repressors or activate Hh target genes, including Ptch1 and Gli1. SPOP is unable to bind Gli1 and does not cause its degradation. Sufu does not seem to have a profound effect on endogenous Gli1, Gli2 or Gli3 nuclear-cytoplasmic shuttling. Ci, Cubitus interruptus; Cul3, Cullin3; FL, full-length; Hh, Hedgehog; HIB, Hedgehog-induced MATH and BTB domain-containing protein; Ptc/Ptch1, Patched; R, repressor; SPOP, Speckle-type POZ protein; Su(fu)/Sufu, Suppressor of fused.