ArticleCell research2022
Cholesterylation of Smoothened is a calcium-accelerated autoreaction involving an intramolecular ester intermediate.
Article in Cell research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 33 citations in OpenAlex.
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- A Modular Bioinstructive Platform Reveals Mechanistic Insights into Additive-Free, Topography-Driven Osteogenesis.Advanced healthcare materials · 2026Article
- Cancer Cell-Intrinsic Cholesterol Induces Lipid-Associated Macrophage Differentiation via SP1 Palmitoylation to Promote Prostate Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cholesterol sensing by the SCAP-FAM134B complex regulates ER-phagy and STING innate immunity.Nature cell biology · 2025Article
- Genome-wide identification and functional characterization of GPCR family genes reveal their key roles in the vitellarium development and egg production in Schistosoma japonicum.Parasites & vectors · 2025Article
- A Novel HeterozygousPhenomics (Cham, Switzerland) · 2025Article
- Regulation of autophagy by protein lipidation.Advanced biotechnology · 2024Review
- Hyperactivation of SREBP induces pannexin-1-dependent lytic cell death.Journal of lipid research · 2024Article
- Fatty acid-binding proteins 3, 7, and 8 bind cholesterol and facilitate its egress from lysosomes.The Journal of cell biology · 2024Article
- Protein lipidation in health and disease: molecular basis, physiological function and pathological implication.Signal transduction and targeted therapy · 2024Review
- Pharmacological targeting of smoothened receptor cysteine-rich domain by Budesonide promotesFrontiers in molecular neuroscience · 2024Article
- Bile acids-mediated intracellular cholesterol transport promotes intestinal cholesterol absorption and NPC1L1 recycling.Nature communications · 2023Article
- Cellular and molecular mechanisms of Hedgehog signalling.Nature reviews. Molecular cell biology · 2023Review
- Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.Signal transduction and targeted therapy · 2023Review
- Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies.Signal transduction and targeted therapy · 2023Review
- GRAMD1/ASTER-mediated cholesterol transport promotes Smoothened cholesterylation at the endoplasmic reticulum.The EMBO journal · 2023Article
- Towards Precision Oncology: The Role of Smoothened and Its Variants in Cancer.Journal of personalized medicine · 2022Review
- The cation-π interaction in cysteine-rich domain of Smoothened is critical for its cholesterylation and function.Acta biochimica et biophysica Sinica · 2022Article
- Arih2 regulates Hedgehog signaling through smoothened ubiquitylation and ER-associated degradation.Journal of cell science · 2022Article
- Hedgehog signaling and its molecular perspective with cholesterol: a comprehensive review.Cellular and molecular life sciences : CMLS · 2022Review
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hedgehog (Hh) is a morphogen that binds to its receptor Patched 1 and activates Smoothened (SMO), thereby governing embryonic development and postnatal tissue homeostasis. Cholesterol can bind and covalently conjugate to the luminal cysteine-rich domain (CRD) of human SMO at the D95 residue (D99 in mouse). The reaction mechanism and biological function of SMO cholesterylation have not been elucidated. Here, we show that the SMO-CRD undergoes auto-cholesterylation which is boosted by calcium and involves an intramolecular ester intermediate. In cells, Hh stimulation elevates local calcium concentration in the SMO-localized endosomes through store-operated calcium entry. In addition, we identify the signaling-incompetent SMO D95E mutation, and the D95E mutant SMO can bind cholesterol but cannot be modified or activated by cholesterol. The homozygous Smo
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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.