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Nat Chem Biol. 2013 Apr;9(4):247-9. doi: 10.1038/nchembio.1184. Epub 2013 Feb 17.

Inhibitors of Hedgehog acyltransferase block Sonic Hedgehog signaling.

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1
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

Abstract

Inhibition of Sonic hedgehog (Shh) signaling is of great clinical interest. Here we exploit Hedgehog acyltransferase (Hhat)-mediated Shh palmitoylation, a modification critical for Shh signaling, as a new target for Shh pathway inhibition. A target-oriented high-throughput screen was used to identify small-molecule inhibitors of Hhat. In cells, these Hhat inhibitors specifically block Shh palmitoylation and inhibit autocrine and paracrine Shh signaling.

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PMID:
23416332
PMCID:
PMC3604071
DOI:
10.1038/nchembio.1184
[Indexed for MEDLINE]
Free PMC Article
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