ArticleDevelopmental cell2016
Regulation of Smoothened Trafficking and Hedgehog Signaling by the SUMO Pathway.
Article in Developmental cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 62 citations in OpenAlex.
- New Insights into TFEB SUMOylation and Its Role in Lipid Metabolism and Cardiovascular Disease.International journal of molecular sciences · 2025Review
- Phosphorylation-induced SUMOylation promotes Ulk4 condensation at the ciliary tip to transduce Hedgehog signal.Journal of cell science · 2025Article
- SUMOylation modulates the dual functions of Krüppel homolog 1 in transcriptional regulation of Broad-Complex expression.Journal of advanced research · 2025Article
- Post-Translational Modifications in Cilia and Ciliopathies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Morphogen-induced kinase condensates transduce Hh signal by allosterically activating Gli.Science advances · 2025Article
- Cell-Based Assays to Study SUMOylation in Drosophila.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Molecular characteristics and cancer immunity of LRP1B and its relationship with the Hedgehog signaling pathway in colorectal cancer.Frontiers in immunology · 2025Article
- Advances in the anti-tumor mechanisms of saikosaponin D.Pharmacological reports : PR · 2024Review
- TFEB SUMOylation in macrophages accelerates atherosclerosis by promoting the formation of foam cells through inhibiting lysosomal activity.Cellular and molecular life sciences : CMLS · 2023Article
- GRAMD1/ASTER-mediated cholesterol transport promotes Smoothened cholesterylation at the endoplasmic reticulum.The EMBO journal · 2023Article
- EVC-EVC2 complex stability and ciliary targeting are regulated by modification with ubiquitin and SUMO.Frontiers in cell and developmental biology · 2023Article
- Dose-dependent phosphorylation and activation of Hh pathway transcription factors.Life science alliance · 2022Article
- 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
- Influence of Sox protein SUMOylation on neural development and regeneration.Neural regeneration research · 2022Review
- Regulation of Smoothened Trafficking and Abundance in Hedgehog Signaling.Frontiers in cell and developmental biology · 2022Review
- Cell-Based Assays for Smoothened Ubiquitination and Sumoylation.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Regulation of Hedgehog Signal Transduction by Ubiquitination and Deubiquitination.International journal of molecular sciences · 2021Review
- Regulation of Serotonin 1A Receptor SUMOylation by SENP2 and PIASxα.International journal of molecular sciences · 2021Article
- An updated SYSCILIA gold standard (SCGSv2) of known ciliary genes, revealing the vast progress that has been made in the cilia research field.Molecular biology of the cell · 2021Review
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7 authors at 1 institution in 1 country.
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Abstract
Hedgehog (Hh) signaling plays a central role in development and diseases. Hh activates its signal transducer and GPCR-family protein Smoothened (Smo) by inducing Smo phosphorylation, but whether Smo is activated through other post-translational modifications remains unexplored. Here we show that sumoylation acts in parallel with phosphorylation to promote Smo cell-surface expression and Hh signaling. We find that Hh stimulates Smo sumoylation by dissociating it from a desumoylation enzyme Ulp1. Sumoylation of Smo in turn recruits a deubiquitinase UBPY/USP8 to antagonize Smo ubiquitination and degradation, leading to its cell-surface accumulation and elevated Hh pathway activity. We also provide evidence that Shh stimulates sumoylation of mammalian Smo (mSmo) and that sumoylation promotes ciliary localization of mSmo and Shh pathway activity. Our findings reveal a conserved mechanism whereby the SUMO pathway promotes Hh signaling by regulating Smo subcellular localization and shed light on how sumoylation regulates membrane protein trafficking.
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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.