ArticleChemistry & biology2014
The Hedgehog pathway effector smoothened exhibits signaling competency in the absence of ciliary accumulation.
Article in Chemistry & biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed.
- Convergent mechanisms in Wnt and Hedgehog signaling.Science signaling · 2026Review
- Absence of the primary cilia formation gene Talpid3 impairs muscle stem cell function.Communications biology · 2023Article
- Primary cilia control oligodendrocyte precursor cell proliferation in white matter injury via Hedgehog-independent CREB signaling.Cell reports · 2023Article
- Cellular and molecular mechanisms of Hedgehog signalling.Nature reviews. Molecular cell biology · 2023Review
- GLI3 regulates muscle stem cell entry into GNature communications · 2022Article
- TMED2 binding restricts SMO to the ER and Golgi compartments.PLoS biology · 2022Article
- Article
- Hypomorphic Smo mutant with inefficient ciliary enrichment disrupts the highest level of vertebrate Hedgehog response.Developmental biology · 2018Article
- A synthetic combinatorial approach to disabling deviant Hedgehog signaling.Scientific reports · 2018Article
- A Flow Cytometry-Based Approach for the Isolation and Characterization of Neural Stem Cell Primary Cilia.Frontiers in cellular neuroscience · 2018Article
- Regulation of Gli ciliary localization and Hedgehog signaling by the PY-NLS/karyopherin-β2 nuclear import system.PLoS biology · 2017Article
- Regulation of Smoothened Phosphorylation and High-Level Hedgehog Signaling Activity by a Plasma Membrane Associated Kinase.PLoS biology · 2016Article
- Dendrosomatic Sonic Hedgehog Signaling in Hippocampal Neurons Regulates Axon Elongation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Hedgehog and Resident Vascular Stem Cell Fate.Stem cells international · 2015Review
- Synthetic Small Molecule Inhibitors of Hh Signaling As Anti-Cancer Chemotherapeutics.Current medicinal chemistry · 2015Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors.
Funding
Abstract
Misactivation of the seven-transmembrane protein Smoothened (Smo) is frequently associated with basal cell carcinoma and medulloblastoma. Cellular exposure to secreted Hedgehog (Hh) protein or oncogenic mutations in Hh pathway components induces Smo accumulation in the primary cilium, an antenna-like organelle with mostly unknown cellular functions. Despite the data supporting an indispensable role of the primary cilium in Smo activation, the mechanistic underpinnings of this dependency remain unclear. Using a cell-membrane-impermeable Smo antagonist (IHR-1), we demonstrate that Smo supplied with a synthetic agonist or activated with oncogenic mutations can signal without ciliary accumulation. Similarly, cells with compromised ciliary Smo trafficking due to loss of the phosphatidylinositol-4-phosphate 3-kinase (PI3K)-C2α retain transcriptional response to an exogenously supplied Smo agonist. These observations suggest that assembly of a Smo-signaling complex in the primary cilium is not a prerequisite for Hh pathway activation driven by Smo agonists or oncogenic Smo molecules.
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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.