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Cancers 2015, 7(4), 2037-2053; doi:10.3390/cancers7040875

Hedgehog Cholesterolysis: Specialized Gatekeeper to Oncogenic Signaling

1
Chemistry Department, Binghamton University 4400 Vestal Parkway East, Binghamton, NY 13902, USA
2
Biology Department, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY 12180, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Hui-Wen Lo
Received: 14 August 2015 / Revised: 22 September 2015 / Accepted: 28 September 2015 / Published: 14 October 2015
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Abstract

Discussions of therapeutic suppression of hedgehog (Hh) signaling almost exclusively focus on receptor antagonism; however, hedgehog’s biosynthesis represents a unique and potentially targetable aspect of this oncogenic signaling pathway. Here, we review a key biosynthetic step called cholesterolysis from the perspectives of structure/function and small molecule inhibition. Cholesterolysis, also called cholesteroylation, generates cholesterol-modified Hh ligand via autoprocessing of a hedgehog precursor protein. Post-translational modification by cholesterol appears to be restricted to proteins in the hedgehog family. The transformation is essential for Hh biological activity and upstream of signaling events. Despite its decisive role in generating ligand, cholesterolysis remains conspicuously unexplored as a therapeutic target. View Full-Text
Keywords: hedgehog; autoprocessing; cholesterol; cancer; cholesterolysis; cholesteroylation; signaling hedgehog; autoprocessing; cholesterol; cancer; cholesterolysis; cholesteroylation; signaling
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Callahan, B.P.; Wang, C. Hedgehog Cholesterolysis: Specialized Gatekeeper to Oncogenic Signaling. Cancers 2015, 7, 2037-2053.

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