title: 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.
authors: Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors: Elissaveta
authors: E
authors: Petrova
authors: Jessica
authors: J
authors: Rios-Esteves
authors: Ouathek
authors: O
authors: Ouerfelli
authors: J Fraser
authors: JF
authors: Glickman
authors: Marilyn D
authors: MD
authors: Resh
mesh_terms: D000217:Acyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D057166:High-Throughput Screening Assays; D006801:Humans; D054878:Lipoylation; D008156:Luciferases; D051379:Mice; D046328:Porcupines; D015398:Signal Transduction / Q000187:drug effects*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D004791:Enzyme Inhibitors; D053823:Hedgehog Proteins; D054852:Small Molecule Libraries; D008156:Luciferases; D000217:Acyltransferases