ArticleCell research2012
Smoothened transduces Hedgehog signal by forming a complex with Evc/Evc2.
Article in Cell research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 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
70 citing papers in PubMed, 109 citations in OpenAlex.
- Genetic Parameters and Genome-Wide Association Analysis of Reproductive and Calving Traits in Jersey Cattle.Animals : an open access journal from MDPI · 2026Article
- EVC protein regulates Sonic hedgehog signaling during human intervertebral disc development and degeneration.iScience · 2026Article
- Oncogenic activation of EVC/EVC2 defines a therapeutically targetable subset of acute myeloid leukemia.Leukemia · 2026Article
- Identification of a NovelGenes · 2025Article
- Multifaceted roles of sonic hedgehog signaling in mammalian inner ear development.Developmental biology · 2025Review
- Epigenetic priming of neural progenitors by Notch enhances Sonic hedgehog signaling and establishes gliogenic competence.Genes & development · 2025Article
- Deciphering the molecular drivers for cashmere/pashmina fiber production in goats: a comprehensive review.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Hedgehog Signaling Pathway in Fibrosis and Targeted Therapies.Biomolecules · 2024Review
- Article
- Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.Signal transduction and targeted therapy · 2023Review
- Identification of Compound HeterozygousGenes · 2023Article
- Understanding the Roles of the Hedgehog Signaling Pathway during T-Cell Lymphopoiesis and in T-Cell Acute Lymphoblastic Leukemia (T-ALL).International journal of molecular sciences · 2023Review
- EVC-EVC2 complex stability and ciliary targeting are regulated by modification with ubiquitin and SUMO.Frontiers in cell and developmental biology · 2023Article
- Towards Precision Oncology: The Role of Smoothened and Its Variants in Cancer.Journal of personalized medicine · 2022Review
- Hedgehog signaling mechanism and role in cancer.Seminars in cancer biology · 2022Review
- Article
- Canonical Hedgehog Pathway and Noncanonical GLI Transcription Factor Activation in Cancer.Cells · 2022Review
- The Emerging Role of Hedgehog Signaling in Viral Infections.Frontiers in microbiology · 2022Review
- Review
- Hedgehog Signaling: Implications in Cancers and Viral Infections.International journal of molecular sciences · 2021Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Hedgehog (Hh) signaling plays pivotal roles in embryonic development and adult tissue homeostasis in species ranging from Drosophila to mammals. The Hh signal is transduced by Smoothened (Smo), a seven-transmembrane protein related to G protein coupled receptors. Despite a conserved mechanism by which Hh activates Smo in Drosophila and mammals, how mammalian Hh signal is transduced from Smo to the Gli transcription factors is poorly understood. Here, we provide evidence that two ciliary proteins, Evc and Evc2, the products of human disease genes responsible for the Ellis-van Creveld syndrome, act downstream of Smo to transduce the Hh signal. We found that loss of Evc/Evc2 does not affect Sonic Hedgehog-induced Smo phosphorylation and ciliary localization but impedes Hh pathway activation mediated by constitutively active forms of Smo. Evc/Evc2 are dispensable for the constitutive Gli activity in Sufu(-/-) cells, suggesting that Evc/Evc2 act upstream of Sufu to promote Gli activation. Furthermore, we demonstrated that Hh stimulates binding of Evc/Evc2 to Smo depending on phosphorylation of the Smo C-terminal intracellular tail and that the binding is abolished in Kif3a(-/-) cilium-deficient cells. We propose that Hh activates Smo by inducing its phosphorylation, which recruits Evc/Evc2 to activate Gli proteins by antagonizing Sufu in the primary cilia.
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What OpenQuestion holds
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.