ArticleScience advances2025
Morphogen-induced kinase condensates transduce Hh signal by allosterically activating Gli.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Targeting Gli1Stem cell reviews and reports · 2026Review
- PI3K/AKT signaling pathway: molecular crossroads in tumorigenesis and therapeutic innovation.Signal transduction and targeted therapy · 2026Review
- Contemporary design of small-molecule kinase modulators: orthosteric, allosteric and induced-proximity strategies.Nature reviews. Drug discovery · 2026Review
- Phosphorylation-induced SUMOylation promotes Ulk4 condensation at the ciliary tip to transduce Hedgehog signal.Journal of cell science · 2025Article
- Hedgehog-stimulated phosphorylation at multiple sites activates Ci by altering Ci-Ci interfaces without full Suppressor of Fused dissociation.PLoS biology · 2025Article
- Physiological analysis of the mechanism of Ci transcription factor activation through multiple Fused phosphorylation sites in Hedgehog signal transduction.bioRxiv : the preprint server for biology · 2025Article
- Cell-Based Assays to Study SUMOylation in Drosophila.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Advances in the role of the IGF signaling system in myelodysplastic syndromes and acute myeloid leukemia.Frontiers in oncology · 2025Review
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Authors and funding
4 authors.
Funding
Abstract
Hedgehog (Hh) morphogen governs embryonic development and tissue homeostasis through the Ci/Gli family transcription factors. Here we report that Hh induces phase separation of the fused (Fu)/Ulk family kinases to allosterically regulate Ci/Gli. We find that Hh-induced phosphorylation of Fu/Ulk3 promotes SUMOylation of their inverted phosphorylation-dependent SUMOylation motifs. Subsequent interaction between SUMO and SUMO-interacting motif drives Fu/Ulk3 self-assembly to form biomolecular condensates that recruit Ci-Sufu and Gli-Sufu in the cytoplasm and primary cilium, respectively. Within the condensates, Fu/Ulk3 undergoes a conformational change to expose Ci/Gli for Fu/Ulk3-mediated phosphorylation and activation, leading to gradual accumulation of nuclear Ci
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