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Hedgehog Cholesterolysis: Specialized Gatekeeper to Oncogenic Signaling.

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.

SUBMITTER: Callahan BP

PROVIDER: S-EPMC4695875 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Hedgehog Cholesterolysis: Specialized Gatekeeper to Oncogenic Signaling.

Callahan Brian P BP Wang Chunyu C

Cancers 20151014 4

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 p ...[more]

PMID: 26473928

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