ArticleScience advances2020
Synthetic lethality by targeting the RUVBL1/2-TTT complex in mTORC1-hyperactive cancer cells.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- EARLY ABORTION 1 is an evolutionarily conserved gene required for plant reproduction.Journal of experimental botany · 2026Article
- Targeting RuvBL1 disrupts mitochondrial metabolism and structure in hepatocellular carcinoma.JHEP reports : innovation in hepatology · 2026Article
- TELO2-interacting protein 1 (TTI1), a novel Wnt/β-catenin target gene, decreases chemo-sensitivity in colorectal cancer by modulating DNA damage responses.Molecular biomedicine · 2026Article
- Article
- Development and Validation of Prognostic Characteristics Associated With Chromatin Remodeling-Related Genes in Ovarian Cancer.Cancer medicine · 2025Article
- RuvBL1/2 reduce toxic dipeptide repeat protein burden in multiple models of C9orf72-ALS/FTD.Life science alliance · 2025Article
- RUVBL1/2 Blockade Targets YTHDF1 Activity to Suppress m6A-Dependent Oncogenic Translation and Colorectal Tumorigenesis.Cancer research · 2024Article
- NPAS2 dampens chemo-sensitivity of lung adenocarcinoma cells by enhancing DNA damage repair.Cell death & disease · 2024Article
- Maturation and Assembly of mTOR Complexes by the HSP90-R2TP-TTT Chaperone System: Molecular Insights and Mechanisms.Sub-cellular biochemistry · 2024Review
- Combined CRISPRi and proteomics screening reveal a cohesin-CTCF-bound allele contributing to increased expression of RUVBL1 and prostate cancer progression.American journal of human genetics · 2023Article
- The Emerging Role of Chromatin Remodeling Complexes in Ovarian Cancer.International journal of molecular sciences · 2022Review
- The Role of Hsp90-R2TP in Macromolecular Complex Assembly and Stabilization.Biomolecules · 2022Review
- Functional foods with antiviral activity.Food science and biotechnology · 2022Review
- Hippocalcin-Like 1 blunts liver lipid metabolism to suppress tumorigenesis via directly targeting RUVBL1-mTOR signaling.Theranostics · 2022Article
- Article
- Oral Administration ofAntioxidants (Basel, Switzerland) · 2021Article
- A chemical genetics approach to examine the functions of AAA proteins.Nature structural & molecular biology · 2021Article
- RuvBL1 Maintains Resistance to TRAIL-Induced Apoptosis by Suppressing c-Jun/AP-1 Activity in Non-Small Cell Lung Cancer.Frontiers in oncology · 2021Article
- Piperlongumine Is an NLRP3 Inhibitor With Anti-inflammatory Activity.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 4 countries.
Funding
Abstract
Despite considerable efforts, mTOR inhibitors have produced limited success in the clinic. To define the vulnerabilities of mTORC1-addicted cancer cells and to find previously unknown therapeutic targets, we investigated the mechanism of piperlongumine, a small molecule identified in a chemical library screen to specifically target cancer cells with a hyperactive mTORC1 phenotype. Sensitivity to piperlongumine was dependent on its ability to suppress RUVBL1/2-TTT, a complex involved in chromatin remodeling and DNA repair. Cancer cells with high mTORC1 activity are subjected to higher levels of DNA damage stress via c-Myc and displayed an increased dependency on RUVBL1/2 for survival and counteracting genotoxic stress. Examination of clinical cancer tissues also demonstrated that high mTORC1 activity was accompanied by high RUVBL2 expression. Our findings reveal a previously unknown role for RUVBL1/2 in cell survival, where it acts as a functional chaperone to mitigate stress levels induced in the mTORC1-Myc-DNA damage axis.
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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.