ArticleProceedings of the National Academy of Sciences of the United States of America2021
RAS interaction with Sin1 is dispensable for mTORC2 assembly and activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 38 citations in OpenAlex.
- GDP-Loaded K-Ras Transiently Binds to Effector B-Raf RBD, Mirroring the Structure of the Active GTP-Loaded Complex.Journal of the American Chemical Society · 2026Article
- Development of a SIN1 Targeting Inhibitor as a Novel Therapeutic Approach for the Treatment of Malignancies.Molecular cancer therapeutics · 2026Article
- Revisiting RAS family GTPase signaling: effector selectivity and oncogenic bypass.The Biochemical journal · 2026Review
- Structural basis for the recruitment and selective phosphorylation of Akt by mTORC2.Science (New York, N.Y.) · 2026Article
- Structure of SHOC2-KRAS-PP1C complex reveals RAS isoform-specific determinants and insights into targeting complex assembly by RAS inhibitors.Nature communications · 2026Article
- SIN1 facilitates glioma progression and is associated with the KRAS/ERK pathway.Journal of neuro-oncology · 2025Article
- Article
- The differential interactomes of the KRAS splice variants identify BIRC6 as a ubiquitin ligase for KRAS4A.Cell reports · 2025Article
- Structural insights into isoform-specific RAS-PI3Kα interactions and the role of RAS in PI3Kα activation.Nature communications · 2025Article
- Making PI3K superfamily enzymes run faster.Advances in biological regulation · 2025Review
- Motif-guided identification of KRAS-interacting proteins.BMC biology · 2024Article
- RAS signaling in carcinogenesis, cancer therapy and resistance mechanisms.Journal of hematology & oncology · 2024Review
- Functional and structural insights into RAS effector proteins.Molecular cell · 2024Review
- Comparative analysis of KRAS4a and KRAS4b splice variants reveals distinctive structural and functional properties.Science advances · 2024Article
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- The allosteric mechanism of mTOR activation can inform bitopic inhibitor optimization.Chemical science · 2024Article
- Crystallographic Studies of KRAS in Complex with Small Molecules and RAS-Binding Proteins.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Unmasking the tumourigenic role of SIN1/MAPKAP1 in the mTOR complex 2.Clinical and translational medicine · 2023Review
- Differential functions of the KRAS splice variants.Biochemical Society transactions · 2023Review
- Origin and Evolution of RAS Membrane Targeting.Oncogene · 2023Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
RAS proteins are molecular switches that interact with effector proteins when bound to guanosine triphosphate, stimulating downstream signaling in response to multiple stimuli. Although several canonical downstream effectors have been extensively studied and tested as potential targets for RAS-driven cancers, many of these remain poorly characterized. In this study, we undertook a biochemical and structural approach to further study the role of Sin1 as a RAS effector. Sin1 interacted predominantly with KRAS isoform 4A in cells through an atypical RAS-binding domain that we have characterized by X-ray crystallography. Despite the essential role of Sin1 in the assembly and activity of mTORC2, we find that the interaction with RAS is not required for these functions. Cells and mice expressing a mutant of Sin1 that is unable to bind RAS are proficient for activation and assembly of mTORC2. Our results suggest that Sin1 is a bona fide RAS effector that regulates downstream signaling in an mTORC2-independent manner.
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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.