Complex interplay between RAS GTPases and RASSF effectors regulates subcellular localization of YAP.
| Autor: | Singh S; Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, H3T 1J4, Canada., Bernal Astrain G; Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, H3T 1J4, Canada., Hincapie AM; Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC, H3A 1A3, Canada., Goudreault M; Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, H3T 1J4, Canada., Smith MJ; Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, H3T 1J4, Canada. matthew.james.smith@umontreal.ca.; Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montréal, QC, H3T 1J4, Canada. matthew.james.smith@umontreal.ca. |
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| Jazyk: | angličtina |
| Zdroj: | EMBO reports [EMBO Rep] 2024 Aug; Vol. 25 (8), pp. 3574-3600. Date of Electronic Publication: 2024 Jul 15. |
| DOI: | 10.1038/s44319-024-00203-9 |
| Abstrakt: | RAS GTPases bind effectors to convert upstream cues to changes in cellular function. Effectors of classical H/K/NRAS are defined by RBD/RA domains which recognize the GTP-bound conformation of these GTPases, yet the specificity of RBD/RAs for over 160 RAS superfamily proteins remains poorly explored. We have systematically mapped interactions between BRAF and four RASSF effectors, the largest family of RA-containing proteins, with all RAS, RHO and ARF small GTPases. 39 validated complexes reveal plasticity in RASSF binding, while BRAF demonstrates tight specificity for classical H/K/NRAS. Complex between RASSF5 and diverse RAS GTPases at the plasma membrane can activate Hippo signalling and sequester YAP in the cytosol. RASSF8 undergoes liquid-liquid phase separation and resides in YAP-associated membraneless condensates, which also engage several RAS and RHO GTPases. The poorly studied RASSF3 has been identified as a first potential effector of mitochondrial MIRO proteins, and its co-expression with these GTPases impacts mitochondria and peroxisome distribution. These data reveal the complex nature of GTPase-effector interactions and show their systematic elucidation can reveal completely novel and biologically relevant cellular processes. (© 2024. The Author(s).) |
| Databáze: | MEDLINE |
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