Phosphorylation-induced SUMOylation promotes Ulk4 condensation at ciliary tip to transduce Hedgehog signal.

ABSTRACT: Hedgehog (Hh) signaling controls embryonic development and adult tissue homeostasis through the Gli family of transcription factors. In vertebrates, Hh signal transduction depends on the primary cilium where Gli is thought to be activated at the ciliary tip, but the underlying mechanism has remained poorly understood. Here we provide evidence that two Unc-51-like kinase (Ulk) family members Stk36 and Ulk4 regulate Gli2 ciliary tip localization and activation through phosphorylation and SUMOylation-mediated condensation in response to Shh. We find that Stk36-mediated phosphorylation of Ulk4 promotes its SUMOylation in response to Shh, and the subsequent interaction between SUMO and a SUMO-Interacting-Motif (SIM) in the C-terminal region of Ulk4 drives Ulk4 self-assembly to form biomolecular

SUBMITTER: Zhou M 

PROVIDER: S-EPMC11601359 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature