ArticleScience signaling2020
Probing the mutational landscape of regulators of G protein signaling proteins in cancer.
Article in Science signaling, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Inhibitory probes for spatiotemporal analysis of GαNature chemical biology · 2026Article
- Expression and prognostic diagnostic significance of RGS gene family in breast cancer.Discover oncology · 2025Article
- G Protein-Coupled Receptor Signaling: Implications and Therapeutic Development Advances in Cancers.MedComm · 2025Review
- Endogenous regulator of G protein signaling 14 (RGS14) blunts cocaine-induced emotionally motivated behaviors in female mice.Addiction neuroscience · 2025Article
- G protein regulation by RGS proteins in the pathophysiology of dilated cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2025Review
- Neuropeptide Precursor VGF Promotes Liver Metastatic Colonization of Gαq Mutant Uveal Melanoma by Facilitating Tumor Microenvironment via Paracrine Loops.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Get Ready to Sharpen Your Tools: A Short Guide to Heterotrimeric G Protein Activity Biosensors.Molecular pharmacology · 2024Review
- Dissecting the molecular basis for the modulation of neurotransmitter GPCR signaling by GINIP.Structure (London, England : 1993) · 2024Article
- Characterization of the Prognosis and Tumor Microenvironment of Cellular Senescence-related Genes through scRNA-seq and Bulk RNA-seq Analysis in GC.Recent patents on anti-cancer drug discovery · 2024Article
- Functional Assessment of Cancer-Linked Mutations in Sensitive Regions of Regulators of G Protein Signaling Predicted by Three-Dimensional Missense Tolerance Ratio Analysis.Molecular pharmacology · 2023Article
- Self-assembled dipeptide based fluorescent nanoparticles as a platform for developing cellular imaging probes and targeted drug delivery chaperones.Nanoscale advances · 2022Article
- Fatty acid metabolism is related to the immune microenvironment changes of gastric cancer and RGS2 is a new tumor biomarker.Frontiers in immunology · 2022Article
- Review
- Residue-level determinants of RGS R4 subfamily GAP activity and specificity towards the GCellular and molecular life sciences : CMLS · 2021Article
- ExploringMicrobial cell (Graz, Austria) · 2021Review
- Stability Analysis of a Signaling Circuit with Dual Species of GTPase Switches.Bulletin of mathematical biology · 2021Article
- Naturally occurring hotspot cancer mutations in GαThe Journal of biological chemistry · 2020Article
- G Protein-Coupled receptors and heterotrimeric G proteins as cancer drivers.FEBS letters · 2020Review
- Article
- Optogenetic activation of heterotrimeric G-proteins by LOV2GIVe, a rationally engineered modular protein.eLife · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The advent of deep-sequencing techniques has revealed that mutations in G protein-coupled receptor (GPCR) signaling pathways in cancer are more prominent than was previously appreciated. An emergent theme is that cancer-associated mutations tend to cause enhanced GPCR pathway activation to favor oncogenicity. Regulators of G protein signaling (RGS) proteins are critical modulators of GPCR signaling that dampen the activity of heterotrimeric G proteins through their GTPase-accelerating protein (GAP) activity, which is conferred by a conserved domain dubbed the "RGS-box." Here, we developed an experimental pipeline to systematically assess the mutational landscape of RGS GAPs in cancer. A pan-cancer bioinformatics analysis of the 20 RGS domains with GAP activity revealed hundreds of low-frequency mutations spread throughout the conserved RGS domain structure with a slight enrichment at positions that interface with G proteins. We empirically tested multiple mutations representing all RGS GAP subfamilies and sampling both G protein interface and noninterface positions with a scalable, yeast-based assay. Last, a subset of mutants was validated using G protein activity biosensors in mammalian cells. Our findings reveal that a sizable fraction of RGS protein mutations leads to a loss of function through various mechanisms, including disruption of the G protein-binding interface, loss of protein stability, or allosteric effects on G protein coupling. Moreover, our results also validate a scalable pipeline for the rapid characterization of cancer-associated mutations in RGS proteins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.