Matches in SemOpenAlex for { <https://semopenalex.org/work/W2040442859> ?p ?o ?g. }
- W2040442859 endingPage "11600" @default.
- W2040442859 startingPage "11591" @default.
- W2040442859 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." @default.
- W2040442859 created "2016-06-24" @default.
- W2040442859 creator A5005099065 @default.
- W2040442859 creator A5008531869 @default.
- W2040442859 creator A5018176610 @default.
- W2040442859 creator A5041913832 @default.
- W2040442859 creator A5046260050 @default.
- W2040442859 creator A5049384131 @default.
- W2040442859 creator A5052442202 @default.
- W2040442859 creator A5057884790 @default.
- W2040442859 creator A5062852461 @default.
- W2040442859 creator A5073832633 @default.
- W2040442859 creator A5073868054 @default.
- W2040442859 date "2015-05-01" @default.
- W2040442859 modified "2023-10-10" @default.
- W2040442859 title "Zinc Inhibits Hedgehog Autoprocessing" @default.
- W2040442859 cites W1840010975 @default.
- W2040442859 cites W1963493384 @default.
- W2040442859 cites W1965532980 @default.
- W2040442859 cites W1965740555 @default.
- W2040442859 cites W1976814871 @default.
- W2040442859 cites W1983594598 @default.
- W2040442859 cites W1984222668 @default.
- W2040442859 cites W1985170396 @default.
- W2040442859 cites W1990210405 @default.
- W2040442859 cites W1993416164 @default.
- W2040442859 cites W1995748038 @default.
- W2040442859 cites W1996218285 @default.
- W2040442859 cites W2005622158 @default.
- W2040442859 cites W2008727413 @default.
- W2040442859 cites W2010246526 @default.
- W2040442859 cites W2015296197 @default.
- W2040442859 cites W2017161894 @default.
- W2040442859 cites W2017774881 @default.
- W2040442859 cites W2019479921 @default.
- W2040442859 cites W2030943228 @default.
- W2040442859 cites W2031928696 @default.
- W2040442859 cites W2035232333 @default.
- W2040442859 cites W2042335929 @default.
- W2040442859 cites W2045431166 @default.
- W2040442859 cites W2047698726 @default.
- W2040442859 cites W2055296003 @default.
- W2040442859 cites W2057805778 @default.
- W2040442859 cites W2065074615 @default.
- W2040442859 cites W2068187630 @default.
- W2040442859 cites W2070584671 @default.
- W2040442859 cites W2072595310 @default.
- W2040442859 cites W2073237479 @default.
- W2040442859 cites W2073782996 @default.
- W2040442859 cites W2073847379 @default.
- W2040442859 cites W2078091097 @default.
- W2040442859 cites W2079133664 @default.
- W2040442859 cites W2088342479 @default.
- W2040442859 cites W2088384398 @default.
- W2040442859 cites W2088968757 @default.
- W2040442859 cites W2101662524 @default.
- W2040442859 cites W2103441049 @default.
- W2040442859 cites W2110383903 @default.
- W2040442859 cites W2112310296 @default.
- W2040442859 cites W2114471035 @default.
- W2040442859 cites W2118756200 @default.
- W2040442859 cites W2119734769 @default.
- W2040442859 cites W2131977398 @default.
- W2040442859 cites W2133158330 @default.
- W2040442859 cites W2145447734 @default.
- W2040442859 cites W2146750656 @default.
- W2040442859 cites W2155772315 @default.
- W2040442859 cites W2160372979 @default.
- W2040442859 cites W2161361673 @default.
- W2040442859 cites W2164258188 @default.
- W2040442859 cites W2168338648 @default.
- W2040442859 cites W2169821755 @default.
- W2040442859 cites W2171027019 @default.
- W2040442859 cites W4229861519 @default.
- W2040442859 cites W4297903474 @default.
- W2040442859 doi "https://doi.org/10.1074/jbc.m114.623264" @default.
- W2040442859 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4416862" @default.
- W2040442859 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25787080" @default.
- W2040442859 hasPublicationYear "2015" @default.
- W2040442859 type Work @default.
- W2040442859 sameAs 2040442859 @default.
- W2040442859 citedByCount "15" @default.
- W2040442859 countsByYear W20404428592015 @default.
- W2040442859 countsByYear W20404428592016 @default.
- W2040442859 countsByYear W20404428592017 @default.
- W2040442859 countsByYear W20404428592019 @default.
- W2040442859 countsByYear W20404428592020 @default.
- W2040442859 countsByYear W20404428592021 @default.
- W2040442859 countsByYear W20404428592022 @default.
- W2040442859 crossrefType "journal-article" @default.
- W2040442859 hasAuthorship W2040442859A5005099065 @default.
- W2040442859 hasAuthorship W2040442859A5008531869 @default.
- W2040442859 hasAuthorship W2040442859A5018176610 @default.
- W2040442859 hasAuthorship W2040442859A5041913832 @default.
- W2040442859 hasAuthorship W2040442859A5046260050 @default.
- W2040442859 hasAuthorship W2040442859A5049384131 @default.
- W2040442859 hasAuthorship W2040442859A5052442202 @default.
- W2040442859 hasAuthorship W2040442859A5057884790 @default.