Experimental variables determine the outcome of RAS-RAS interactions
RAS clustering at the cell membrane is critical to activate signaling in cells, but whether this clustering is mediated exclusively by its c-terminal hypervariable region, receives contributions from the G-domain of RAS, and/or is influenced by secondary effectors has been intensely debated. Reports that G-domain mutations do not modulate RAS-RAS interactions have led some to question the validity of previous experiments that indicate the G-domain plays a role in RAS clustering/interactions. Here we reconcile these findings by clarifying the impact of experimental variables, such as protein expression levels, cellular context, RAS zygosity, and secondary effector interactions on RAS clustering. Lack of control over these variables impacts the results using G-domain mutations across various assay systems and can lead to unsound conclusions.
Authors
- Chiara Ambrogio (ORCID: https://orcid.org/0000-0003-4122-701X)
- Kenneth D. Westover (ORCID: https://orcid.org/0000-0003-3653-5923)
- Christel Poujol (ORCID: https://orcid.org/0000-0002-5222-9064)
- David Santamarı́a (ORCID: https://orcid.org/0000-0002-4711-3569)
- Monte M. Winslow (ORCID: https://orcid.org/0000-0002-5730-9573)
- Yibing Shan (ORCID: https://orcid.org/0000-0002-3865-8110)
- Zhiwei Zhou (ORCID: https://orcid.org/0000-0002-1249-6870)
- Ewa Berlinska (ORCID: https://orcid.org/0009-0008-4395-6092)
- Jonas N. Kapp (ORCID: https://orcid.org/0000-0002-7308-559X)
- Sandra Vietti Michelina (ORCID: https://orcid.org/0009-0007-3777-4906)
- Andreas Plückthun (ORCID: https://orcid.org/0000-0003-4191-5306)
- Xing-Xiao Li
- Tra Ly Nguyen
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université de Bordeaux (FR)
- Inserm (FR)
- Universidad de Salamanca (ES)
- University of Zurich (CH)
- Southwestern Medical Center (US)
- Bordeaux Population Health (FR)
- Centro de Investigación del Cáncer (ES)
- Institut Européen de Chimie et Biologie (FR)
- Cancer Research Foundation (US)
- Bordeaux Imaging Center (FR)
- BoRdeaux Institute of onCology (FR)
- University of Turin (IT)
- The University of Texas Southwestern Medical Center (US)
- Stanford University (US)
Publication Details
- Journal
- Journal of Biological Chemistry
- Published
- 2024-10-05
- DOI
- https://doi.org/10.1016/j.jbc.2024.107859
- Citations
- 6
- Primary Topic
- RNA Research and Splicing
- Type
- article
- Field-Weighted Citation Impact
- 1.40
Funders
- Cancer Prevention and Research Institute of Texas
- European Commission
- Ministerio de Ciencia e Innovación
- Associazione Italiana per la Ricerca sul Cancro
- Institut National Du Cancer
- Swiss Cancer Research Foundation
- National Institutes of Health