Reference : Drug targeting opportunities en route to Ras nanoclusters.
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/10993/50453
Drug targeting opportunities en route to Ras nanoclusters.
English
Pavic, Karolina mailto [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)]
Chippalkatti, Rohan mailto [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)]
Abankwa, Daniel mailto [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)]
2022
Advances in cancer research
153
63-99
Yes
International
0065-230X
2162-5557
United States
[en] Drug development ; Nanocluster ; Polarized cell ; Ras ; Trafficking chaperones
[en] Disruption of the native membrane organization of Ras by the farnesyltransferase inhibitor tipifarnib in the late 1990s constituted the first indirect approach to drug target Ras. Since then, our understanding of how dynamically Ras shuttles between subcellular locations has changed significantly. Ras proteins have to arrive at the plasma membrane for efficient MAPK-signal propagation. On the plasma membrane Ras proteins are organized into isoform specific proteo-lipid assemblies called nanocluster. Recent evidence suggests that Ras nanocluster have a specific lipid composition, which supports the recruitment of effectors such as Raf. Conversely, effectors possess lipid-recognition motifs, which appear to serve as co-incidence detectors for the lipid domain of a given Ras isoform. Evidence suggests that dimeric Raf proteins then co-assemble dimeric Ras in an immobile complex, thus forming the minimal unit of an active nanocluster. Here we review established and novel trafficking chaperones and trafficking factors of Ras, along with the set of lipid and protein modulators of Ras nanoclustering. We highlight drug targeting approaches and opportunities against these determinants of functional Ras membrane organization. Finally, we reflect on implications for Ras signaling in polarized cells, such as epithelia, which are a common origin of tumorigenesis.
Researchers
http://hdl.handle.net/10993/50453
Copyright © 2022 Elsevier Inc. All rights reserved.
FnR ; FNR14174764 > Daniel Abankwa > RAS-NANOME > Identification And Characterization Of Novel Ras Plasma Membrane Signalling Complex Modulators - The Ras-nanome > 01/10/2020 > 30/09/2023 > 2020

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