The Role of Cholesterol in Activating a Key Cellular Signaling Pathway

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Identifier the_role_of_cholesterol_in_activating_a_key_cellular_signaling_pathway
Title The Role of Cholesterol in Activating a Key Cellular Signaling Pathway
Creator Myers, B.R.; Huntsman Cancer Institute and Department of Oncological Sciences, School of Medicine, University of Utah Health
Subject Diffusion of Innovation; Cholesterol; Smoothened Receptor; Receptors, CXCR4; Signal Transduction; Hedgehog Proteins; Binding Sites; Solubility; Crystallography, X-Ray ; Antineoplastic Agents; Knowledge Discovery
Keyword Cancer
Image Caption (A) Cholesterol (yellow) binds and activates Smoothened (green) via a tunnel to the membrane inner leaflet (outlined in red.) (B) Clinical anticancer drugs block Smoothened by clashing with and displacing the bound cholesterol, suggesting new strategies to design more effective inhibitors.
Description Hedgehog signaling promotes embryonic development and, when aberrant, can lead to malignancies. The seven-transmembrane transducer Smoothened (SMO) occupies a key node in this pathway and is activated by cholesterol. However, how smoothened binds cholesterol and activates SMO had not been determined. A crystal structure by Myers and colleagues has revealed how cholesterol binds and activates SMO. Remarkably, the cholesterol-binding site resides within a pocket deep inside the seven-transmembrane domain, rather than on a surface location, as proposed previously. This insight suggests new strategies for overcoming clinical resistance to SMO inhibitors.
Relation is Part of 2019
Publisher Spencer S. Eccles Health Sciences Library, University of Utah
Date Digital 2020
Date 2019
Type Image
Format image/jpeg
Rights Management Copyright © 2021, University of Utah, All Rights Reserved
Language eng
ARK ark:/87278/s6bc9nk9
References 1.) Smoothened stimulation by membrane sterols drives Hedgehog pathway activity. Deshpande I, Liang J, Hedeen D, Roberts KJ, Zhang Y, Ha B, Latorraca NR, Faust B, Dror RO, Beachy PA, Myers BR, Manglik A. Nature. 2019 Jul;571(7764):284.
Press Releases and Media Possible ‘Achilles Heel' Discovered in Developing Better Drug Treatment in Cancers with Overactive Smoothened Protein.
Setname ehsl_50disc
Date Created 2020-08-13
Date Modified 2021-05-06
ID 1589360
Reference URL
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