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Zinc inhibits Hedgehog autoprocessing: linking zinc deficiency with Hedgehog activation


, : Zinc inhibits Hedgehog autoprocessing: linking zinc deficiency with Hedgehog activation. Journal of Biological Chemistry 290(18): 11591-11600

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.

US$19.90

PMID: 25787080

DOI: 10.1074/jbc.M114.623264


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Lader, P., F.; Olsen, A.; Jensen, A.; Sveen, J.-Kristian; Fredheim, A.; Enerhaug, B., 2007: Experimental investigation of the interaction between waves and net structures - Damping mechanism. One of the possibilities to expand sea-based fish farming is to move aquaculture installations away from the conflicts of the coastal zone, and into more open ocean locations. However, open ocean aquaculture places different demands on structures...

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Hofman, V.; Ladner, J.; Tran, A.T.; Rampal, A.; Chevallier, A.; Boissy, C.; Michiels, J.F.; de Clercq, A.; Dabis, F.; Hofman, P., 1999: Placental infection in Rwanda: comparison an HIV infected population and a control population. We report an histological study from term placentas of 286 HIV positive women born in Rwanda. We observed chorioamnionitis without any pathogen in 15% of the cases, cocci Gram positive infection in 12 observations and malaria infection in 75% of p...

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Bode, PM.; Bode, HR., 1982: Proportioning a Hydra. American Zoologist, 221: 7-15

Pagnano, P.M.; Pimenta, W.P.; Campos, J.C., 1964: Nevus Fusco-Caeruleus Ophthalmo-Maxillaris Or Ota's Nevus. Revista Paulista de Medicina 65: 124-130

Liébano-Hernández, E.; López-Arellano, M.E.; Vázquez-Prats, V.; Mendoza de Gives, P., 1996: Cryopreservation of infective larvae of Haemonchus contortus. Three cryoprotectants were evaluated for Haemonchus contortus infective (L3) larvae: phosphate saline buffer at pH 7.2 (PBS); 10% dimethyl sulfoxide (DMSO); and 10% glycerol. Fifty thousand infective larvae were placed in each of 10 vials per cryo...

Kelleners T.J.; Sharma R.D.; van Hoffen R.A., 1997: Salinity of drainage water from pipe drains in clay soils. Annual Report - International Institute for Land Reclamation and Improvement (ILRI) 1997: 26-39

Heinmets, F., 1978: Electron reactions with cytochrome c in ethylene glycol water glass at minus 196 celsius. Low temperature .gamma.-irradiation and spectroscopy are used to study electron reactions with [horse heart] cytochrome c in aquo organic glass at -196.degree. C. Spectral data suggest that cytochrome c is reduced by electrons at -196.degree. C. R...