ArticleGenes & development2009
Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved.
Article in Genes & development, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 238 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
238 citing papers in PubMed, 352 citations in OpenAlex.
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- Functional dissection ofProceedings of the National Academy of Sciences of the United States of America · 2026Article
- CMA-mediated USP9X degradation promotes SHH medulloblastoma progression by facilitating SUFU ubiquitination.Clinical and translational medicine · 2026Article
- SPOP and HAUSP bidirectionally regulate LZTS2 ubiquitination to modulate the Wnt pathway.Cell death & disease · 2025Article
- Primary cilia function as hubs for signal transduction.Cell & bioscience · 2025Review
- GliFHV mice: a tool to investigate GLI processing and localization.Development (Cambridge, England) · 2025Article
- Phosphorylation-induced SUMOylation promotes Ulk4 condensation at the ciliary tip to transduce Hedgehog signal.Journal of cell science · 2025Article
- Thymoquinone mediated hedgehog pathway activation and gut microbiota modulation in mouse colitis.Scientific reports · 2025Article
- Hedgehog pathway, cell cycle, and primary cilium.Cell death discovery · 2025Review
- Hedgehog-stimulated phosphorylation at multiple sites activates Ci by altering Ci-Ci interfaces without full Suppressor of Fused dissociation.PLoS biology · 2025Article
- Regulatory mechanisms governing GLI proteins in hedgehog signaling.Anatomical science international · 2025Review
- Cul3 substrate adaptor SPOP targets Nup153 for degradation.Molecular biology of the cell · 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
- Article
- Morphogen-induced kinase condensates transduce Hh signal by allosterically activating Gli.Science advances · 2025Article
- Article
- KIAA0753 enhances osteoblast differentiation suppressed by diabetes.Journal of cellular and molecular medicine · 2024Article
- P4HA2 hydroxylates SUFU to regulate the paracrine Hedgehog signaling and promote B-cell lymphoma progression.Leukemia · 2024Article
- Positive regulation of Hedgehog signaling via phosphorylation of GLI2/GLI3 by DYRK2 kinase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis.Cell discovery · 2024Review
178 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A central question in Hedgehog (Hh) signaling is how evolutionarily conserved components of the pathway might use the primary cilium in mammals but not fly. We focus on Suppressor of fused (Sufu), a major Hh regulator in mammals, and reveal that Sufu controls protein levels of full-length Gli transcription factors, thus affecting the production of Gli activators and repressors essential for graded Hh responses. Surprisingly, despite ciliary localization of most Hh pathway components, regulation of Gli protein levels by Sufu is cilium-independent. We propose that Sufu-dependent processes in Hh signaling are evolutionarily conserved. Consistent with this, Sufu regulates Gli protein levels by antagonizing the activity of Spop, a conserved Gli-degrading factor. Furthermore, addition of zebrafish or fly Sufu restores Gli protein function in Sufu-deficient mammalian cells. In contrast, fly Smo is unable to translocate to the primary cilium and activate the mammalian Hh pathway. We also uncover a novel positive role of Sufu in regulating Hh signaling, resulting from its control of both Gli activator and repressor function. Taken together, these studies delineate important aspects of cilium-dependent and cilium-independent Hh signal transduction and provide significant mechanistic insight into Hh signaling in diverse species.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.