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Inhibitors of Hedgehog acyltransferase block Sonic Hedgehog signaling.

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.

SUBMITTER: Petrova E

PROVIDER: S-EPMC3604071 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Inhibitors of Hedgehog acyltransferase block Sonic Hedgehog signaling.

Petrova Elissaveta E Rios-Esteves Jessica J Ouerfelli Ouathek O Glickman J Fraser JF Resh Marilyn D MD

Nature chemical biology 20130217 4

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. ...[more]

PMID: 23416332

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