ArticleThe Journal of biological chemistry2015
Zinc inhibits Hedgehog autoprocessing: linking zinc deficiency with Hedgehog activation.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The trial behind it
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Who cites it
13 citing papers in PubMed.
- In vitro reconstitution of vertebrate Sonic Hedgehog protein cholesterolysis.bioRxiv : the preprint server for biology · 2026Article
- Hedgehog Autoprocessing: From Structural Mechanisms to Drug Discovery.Frontiers in molecular biosciences · 2022Review
- Inteins as Drug Targets and Therapeutic Tools.Frontiers in molecular biosciences · 2022Review
- Celecoxib alleviates zinc deficiency-promoted colon tumorigenesis through suppressing inflammation.Aging · 2021Article
- Article
- Sterol A-ring plasticity in hedgehog protein cholesterolysis supports a primitive substrate selectivity mechanism.Chemical communications (Cambridge, England) · 2019Article
- Biophysical characterisation of the novel zinc binding property in Suppressor of Fused.Scientific reports · 2017Article
- The miR-183 family cluster alters zinc homeostasis in benign prostate cells, organoids and prostate cancer xenografts.Scientific reports · 2017Article
- Copper and Zinc Homeostasis: Lessons fromFrontiers in genetics · 2017Review
- PEGylation of zinc nanoparticles amplifies their ability to enhance olfactory responses to odorant.PloS one · 2017Article
- Hedgehog Proteins Consume Steroidal CYP17A1 Antagonists: Potential Therapeutic Significance in Advanced Prostate Cancer.ChemMedChem · 2016Article
- A Single Aspartate Coordinates Two Catalytic Steps in Hedgehog Autoprocessing.Journal of the American Chemical Society · 2016Article
- Review
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Zinc is an essential trace element with wide-ranging biological functions, whereas the Hedgehog (Hh) signaling pathway plays crucial roles in both development and disease. Here we show that there is a mechanistic link between zinc and Hh signaling. The upstream activator of Hh signaling, the Hh ligand, originates from Hh autoprocessing, which converts the Hh precursor protein to the Hh ligand. In an in vitro Hh autoprocessing assay we show that zinc inhibits Hh autoprocessing with a Ki of 2 μm. We then demonstrate that zinc inhibits Hh autoprocessing in a cellular environment with experiments in primary rat astrocyte culture. Solution NMR reveals that zinc binds the active site residues of the Hh autoprocessing domain to inhibit autoprocessing, and isothermal titration calorimetry provided the thermodynamics of the binding. In normal physiology, zinc likely acts as a negative regulator of Hh autoprocessing and inhibits the generation of Hh ligand and Hh signaling. In many diseases, zinc deficiency and elevated level of Hh ligand co-exist, including prostate cancer, lung cancer, ovarian cancer, and autism. Our data suggest a causal relationship between zinc deficiency and the overproduction of Hh ligand.
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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.