ArticleScientific reports2017
SUMO regulates the activity of Smoothened and Costal-2 in Drosophila Hedgehog signaling.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Hedgehog signaling mechanism and role in cancer.Seminars in cancer biology · 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 Serotonin 1A Receptor SUMOylation by SENP2 and PIASxα.International journal of molecular sciences · 2021Article
- Review
- Post-Translational Modifications of G Protein-Coupled Receptors Control Cellular Signaling Dynamics in Space and Time.Pharmacological reviews · 2021Review
- SUMOylation in development and neurodegeneration.Development (Cambridge, England) · 2020Review
- miR-135a Inhibits the Invasion and Migration of Esophageal Cancer Stem Cells through the Hedgehog Signaling Pathway by Targeting Smo.Molecular therapy. Nucleic acids · 2020Article
- Proteostasis in the Hedgehog signaling pathway.Seminars in cell & developmental biology · 2019Review
- Regulation of Smoothened ubiquitylation and cell surface expression through a Cul4-DDB1-Gβ E3 ubiquitin ligase complex.Journal of cell science · 2018Article
- SUMOylation controls stem cell proliferation and regional cell death through Hedgehog signaling in planarians.Cellular and molecular life sciences : CMLS · 2018Article
- Hedgehog reciprocally controls trafficking of Smo and Ptc through the Smurf family of E3 ubiquitin ligases.Science signaling · 2018Article
- An intracellular activation of Smoothened that is independent of Hedgehog stimulation inJournal of cell science · 2018Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
In Hedgehog (Hh) signaling, the GPCR-family protein Smoothened (Smo) acts as a signal transducer that is regulated by phosphorylation and ubiquitination, which ultimately change the cell surface accumulation of Smo. However, it is not clear whether Smo is regulated by other post-translational modifications, such as sumoylation. Here, we demonstrate that knockdown of the small ubiquitin-related modifier (SUMO) pathway components Ubc9 (a SUMO-conjugating enzyme E2), PIAS (a SUMO-protein ligase E3), and Smt3 (the SUMO isoform in Drosophila) by RNAi prevents Smo accumulation and alters Smo activity in the wing. We further show that Hh-induced-sumoylation stabilizes Smo, whereas desumoylation by Ulp1 destabilizes Smo in a phosphorylation independent manner. Mechanistically, we discover that excessive Krz, the Drosophila β-arrestin 2, inhibits Smo sumoylation and prevents Smo accumulation through Krz regulatory domain. Krz likely facilitates the interaction between Smo and Ulp1 because knockdown of Krz by RNAi attenuates Smo-Ulp1 interaction. Finally, we provide evidence that Cos2 is also sumoylated, which counteracts its inhibitory role on Smo accumulation in the wing. Taken together, we have uncovered a novel mechanism for Smo activation by sumoylation that is regulated by Hh and Smo interacting proteins.
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