Inhibitors of Hedgehog Acyltransferase Block Sonic Hedgehog Signaling

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 novel target for Shh pathway inhibition. A target-oriented high-throughput screen was used to ident...

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Detalles Bibliográficos
Autores principales: Petrova, Elissaveta, Rios-Esteves, Jessica, Ouerfelli, Ouathek, Glickman, J. Fraser, Resh, Marilyn D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3604071/
https://www.ncbi.nlm.nih.gov/pubmed/23416332
http://dx.doi.org/10.1038/nchembio.1184
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author Petrova, Elissaveta
Rios-Esteves, Jessica
Ouerfelli, Ouathek
Glickman, J. Fraser
Resh, Marilyn D.
author_facet Petrova, Elissaveta
Rios-Esteves, Jessica
Ouerfelli, Ouathek
Glickman, J. Fraser
Resh, Marilyn D.
author_sort Petrova, Elissaveta
collection PubMed
description 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 novel 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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spelling pubmed-36040712013-10-01 Inhibitors of Hedgehog Acyltransferase Block Sonic Hedgehog Signaling Petrova, Elissaveta Rios-Esteves, Jessica Ouerfelli, Ouathek Glickman, J. Fraser Resh, Marilyn D. Nat Chem Biol Article 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 novel 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. 2013-02-17 2013-04 /pmc/articles/PMC3604071/ /pubmed/23416332 http://dx.doi.org/10.1038/nchembio.1184 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Petrova, Elissaveta
Rios-Esteves, Jessica
Ouerfelli, Ouathek
Glickman, J. Fraser
Resh, Marilyn D.
Inhibitors of Hedgehog Acyltransferase Block Sonic Hedgehog Signaling
title Inhibitors of Hedgehog Acyltransferase Block Sonic Hedgehog Signaling
title_full Inhibitors of Hedgehog Acyltransferase Block Sonic Hedgehog Signaling
title_fullStr Inhibitors of Hedgehog Acyltransferase Block Sonic Hedgehog Signaling
title_full_unstemmed Inhibitors of Hedgehog Acyltransferase Block Sonic Hedgehog Signaling
title_short Inhibitors of Hedgehog Acyltransferase Block Sonic Hedgehog Signaling
title_sort inhibitors of hedgehog acyltransferase block sonic hedgehog signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3604071/
https://www.ncbi.nlm.nih.gov/pubmed/23416332
http://dx.doi.org/10.1038/nchembio.1184
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AT glickmanjfraser inhibitorsofhedgehogacyltransferaseblocksonichedgehogsignaling
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