ArticleThe Journal of cell biology2020
Ubiquitin links smoothened to intraflagellar transport to regulate Hedgehog signaling.
Article in The Journal of cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
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Who cites it
62 citing papers in PubMed, 85 citations in OpenAlex.
- Primary cilia: master conductors of cellular communication in development and disease.Nature reviews. Nephrology · 2026Review
- In situ structure of the human ciliary transition zone links linker defects to primary ciliary dyskinesia.Science (New York, N.Y.) · 2026Article
- Structure Makes a Difference: IFT Complex in Ciliary Function and Ciliopathy.Cytoskeleton (Hoboken, N.J.) · 2026Review
- K63-linked ubiquitin chains mark inactive Smoothened for packaging into ciliary extracellular vesicles.bioRxiv : the preprint server for biology · 2026Article
- Article
- Bardet-Biedl syndrome 1 mutations differentially impact BBSome integrity and ciliary trafficking.Cell communication and signaling : CCS · 2026Article
- BBSome: An essential component of hypothalamic regulation of energy homeostasis.Reviews in endocrine & metabolic disorders · 2026Review
- Primary cilia and BBS4 are required for postnatal pituitary development.Developmental biology · 2026Article
- ALIX and ITCH localize to the base of primary cilia and negatively regulate ciliary Polycystin-2 levels.BMC molecular and cell biology · 2026Article
- Trisomy 21 alters ciliary localization of Sonic Hedgehog signaling proteins.bioRxiv : the preprint server for biology · 2026Article
- Article
- Proteome-widebioRxiv : the preprint server for biology · 2025Article
- Implication of GPRASP2 in the Proliferation and Hair Cell-Forming of Cochlear Supporting Cells.Cell proliferation · 2025Article
- Advances in ciliary proteomics - towards cracking the hidden proteome code of cilia.Journal of cell science · 2025Review
- C. elegans: An elegant experimental system for the study of cilia biology.Seminars in cell & developmental biology · 2025Review
- BBSome-Mediated Clearance of Ubiquitinated IMPG2 Defines a Constitutive Ciliary Retrieval Pathway in Photoreceptors.bioRxiv : the preprint server for biology · 2025Article
- G Protein-Coupled Receptor Signal Intersection at the Primary Cilium.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- The intraflagellar transport cycle.Nature reviews. Molecular cell biology · 2025Review
- The O-glycosyltransferase C1GALT1 promotes EWSR1::FLI1 expression and is a therapeutic target for Ewing sarcoma.Nature communications · 2025Article
- Tonic ubiquitination of the central body weight regulator melanocortin receptor 4 (MC4R) promotes its constitutive exit from cilia.PLoS biology · 2025Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
In the absence of Hedgehog ligand, patched-1 (Ptch1) localizes to cilia and prevents ciliary accumulation and activation of smoothened (Smo). Upon ligand binding, Ptch1 is removed from cilia, and Smo is derepressed and accumulates in cilia where it activates signaling. The mechanisms regulating these dynamic movements are not well understood, but defects in intraflagellar transport components, including Ift27 and the BBSome, cause Smo to accumulate in cilia without pathway activation. We find that in the absence of ligand-induced pathway activation, Smo is ubiquitinated and removed from cilia, and this process is dependent on Ift27 and BBSome components. Activation of Hedgehog signaling decreases Smo ubiquitination and ciliary removal, resulting in its accumulation. Blocking ubiquitination of Smo by an E1 ligase inhibitor or by mutating two lysine residues in intracellular loop three causes Smo to aberrantly accumulate in cilia without pathway activation. These data provide a mechanism to control Smo's ciliary level during Hedgehog signaling by regulating the ubiquitination state of the receptor.
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Registered trials
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.