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Lipid Profiles of RAS Nanoclusters Regulate RAS Function

The lipid-anchored RAS (Rat sarcoma) small GTPases (guanosine triphosphate hydrolases) are highly prevalent in human cancer. Traditional strategies of targeting the enzymatic activities of RAS have been shown to be difficult. Alternatively, RAS function and pathology are mostly restricted to nanoclu...

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Detalles Bibliográficos
Autores principales: Zhou, Yong, Hancock, John F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533076/
https://www.ncbi.nlm.nih.gov/pubmed/34680072
http://dx.doi.org/10.3390/biom11101439
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author Zhou, Yong
Hancock, John F.
author_facet Zhou, Yong
Hancock, John F.
author_sort Zhou, Yong
collection PubMed
description The lipid-anchored RAS (Rat sarcoma) small GTPases (guanosine triphosphate hydrolases) are highly prevalent in human cancer. Traditional strategies of targeting the enzymatic activities of RAS have been shown to be difficult. Alternatively, RAS function and pathology are mostly restricted to nanoclusters on the plasma membrane (PM). Lipids are important structural components of these signaling platforms on the PM. However, how RAS nanoclusters selectively enrich distinct lipids in the PM, how different lipids contribute to RAS signaling and oncogenesis and whether the selective lipid sorting of RAS nanoclusters can be targeted have not been well-understood. Latest advances in quantitative super-resolution imaging and molecular dynamic simulations have allowed detailed characterization RAS/lipid interactions. In this review, we discuss the latest findings on the select lipid composition (with headgroup and acyl chain specificities) within RAS nanoclusters, the specific mechanisms for the select lipid sorting of RAS nanoclusters on the PM and how perturbing lipid compositions within RAS nanoclusters impacts RAS function and pathology. We also describe different strategies of manipulating lipid composition within RAS nanoclusters on the PM.
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spelling pubmed-85330762021-10-23 Lipid Profiles of RAS Nanoclusters Regulate RAS Function Zhou, Yong Hancock, John F. Biomolecules Review The lipid-anchored RAS (Rat sarcoma) small GTPases (guanosine triphosphate hydrolases) are highly prevalent in human cancer. Traditional strategies of targeting the enzymatic activities of RAS have been shown to be difficult. Alternatively, RAS function and pathology are mostly restricted to nanoclusters on the plasma membrane (PM). Lipids are important structural components of these signaling platforms on the PM. However, how RAS nanoclusters selectively enrich distinct lipids in the PM, how different lipids contribute to RAS signaling and oncogenesis and whether the selective lipid sorting of RAS nanoclusters can be targeted have not been well-understood. Latest advances in quantitative super-resolution imaging and molecular dynamic simulations have allowed detailed characterization RAS/lipid interactions. In this review, we discuss the latest findings on the select lipid composition (with headgroup and acyl chain specificities) within RAS nanoclusters, the specific mechanisms for the select lipid sorting of RAS nanoclusters on the PM and how perturbing lipid compositions within RAS nanoclusters impacts RAS function and pathology. We also describe different strategies of manipulating lipid composition within RAS nanoclusters on the PM. MDPI 2021-09-30 /pmc/articles/PMC8533076/ /pubmed/34680072 http://dx.doi.org/10.3390/biom11101439 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Zhou, Yong
Hancock, John F.
Lipid Profiles of RAS Nanoclusters Regulate RAS Function
title Lipid Profiles of RAS Nanoclusters Regulate RAS Function
title_full Lipid Profiles of RAS Nanoclusters Regulate RAS Function
title_fullStr Lipid Profiles of RAS Nanoclusters Regulate RAS Function
title_full_unstemmed Lipid Profiles of RAS Nanoclusters Regulate RAS Function
title_short Lipid Profiles of RAS Nanoclusters Regulate RAS Function
title_sort lipid profiles of ras nanoclusters regulate ras function
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533076/
https://www.ncbi.nlm.nih.gov/pubmed/34680072
http://dx.doi.org/10.3390/biom11101439
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