40 Years of RAS—A Historic Overview
Abstract
:1. The Discovery of RAS Genes: From Viruses to Humans and Beyond
1.1. The Retroviral RAS Oncogenes
1.2. The Human RAS Oncogenes
1.3. The RAS Gene Products
1.4. The Universal RAS Superfamily in Eukaryotes
2. The Progress of RAS Biology and Signaling during the 20th Century
2.1. Growth Factors and Their Receptors Activate Cellular RAS
2.2. RAS Activation. The Guanine Nucleotide Exchange Factors (GEFs)
2.3. RAS Inactivation. The GTPase Activating Proteins (GAPs)
2.4. The Link Between Surface Receptors and RAS Activation. The GRB2 Adaptor Proteins
2.5. RAS Functional Domains and Three-Dimensional Structure
2.6. RAS Downstream Effectors and Signaling Pathways
3. Further Advances on RAS Signaling during the 21st Century
3.1. RAS Regulation Through Covalent Modifications
3.2. RAS Inter-Molecular Interactions
3.3. Positive Feedback Loops of RAS Activation
3.4. RAS Signaling from Endomembranes
3.5. Regulation of RAS Expression by Micro RNAs
4. RAS in Physiology and Pathology
4.1. Central Role of RAS Signaling in Physiological Cellular Processes
4.2. Aberrant RAS Signaling in Cancer
4.3. Defective RAS Signaling in Developmental Syndromes
5. Animal Models for the Analysis of RAS Function
5.1. Transgenic Mice
5.2. Knockout Mice
5.3. Functional Specificity/Redundancy of RAS Isoforms
5.4. Mouse Models of RAS-Driven Cancer
5.5. Animal Models of Human RASopathies
6. Therapeutic Approaches to RAS-Driven Cancer
6.1. Blocking RAS Location at the Plasma Membrane
6.2. Inhibiting RAS Downstream Signaling
6.3. Direct RAS Inhibitors
6.4. Future Perspectives on RAS Therapy
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Fernández-Medarde, A.; De Las Rivas, J.; Santos, E. 40 Years of RAS—A Historic Overview. Genes 2021, 12, 681. https://doi.org/10.3390/genes12050681
Fernández-Medarde A, De Las Rivas J, Santos E. 40 Years of RAS—A Historic Overview. Genes. 2021; 12(5):681. https://doi.org/10.3390/genes12050681
Chicago/Turabian StyleFernández-Medarde, Alberto, Javier De Las Rivas, and Eugenio Santos. 2021. "40 Years of RAS—A Historic Overview" Genes 12, no. 5: 681. https://doi.org/10.3390/genes12050681