ArticleNature communications2021
RNF167 activates mTORC1 and promotes tumorigenesis by targeting CASTOR1 for ubiquitination and degradation.
Article in Nature communications, 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, 48 citations in OpenAlex.
- TP53 mutations in triple-negative breast cancer cells confer sensitivity to ASCT2 inhibition via arginine uptake.Cell death & disease · 2026Article
- piR-16404 drives ferroptotic liver injury via CASTOR1/mTORC1/GPX4 dysregulation in HepG2 cells and mice: a novel toxicity mechanism of N, N-dimethylformamide.Archives of toxicology · 2026Article
- The role of L-Arginine metabolism in the hallmarks of cancer as an emerging pathway to drug design.Frontiers in pharmacology · 2026Review
- Gut microbiota-derived arginine metabolism mitigates intestinal ischemia-reperfusion injury.Journal of translational medicine · 2025Article
- Characterization of E1 enzyme dependencies in mutant-UBA1 human cells reveals UBA6 as a novel therapeutic target in VEXAS syndrome.Leukemia · 2025Article
- Upregulating mTOR/S6 K Pathway by CASTOR1 Promotes Astrocyte Proliferation and Myelination in GpamMolecular neurobiology · 2025Article
- Lysosomal quality control Review.Autophagy · 2025Review
- Phosphorylation enhanced OTUD3 deubiquitination ARID3A promotes the progress of cholangiocarcinoma.Oncogene · 2025Article
- PPDPF-mediated regulation of BCAA metabolism enhances mTORC1 activity and drives cholangiocarcinoma progression.Oncogene · 2025Article
- Article
- RNF167 mediates atypical ubiquitylation and degradation of RLRs via two distinct proteolytic pathways.Nature communications · 2025Article
- mTORC1, the maestro of cell metabolism and growth.Genes & development · 2025Review
- Ubiquitination Enzymes in Cancer, Cancer Immune Evasion, and Potential Therapeutic Opportunities.Cells · 2025Review
- CASTOR1 phosphorylation predicts poor survival in male patients with KRAS-mutated lung adenocarcinoma.Cell & bioscience · 2024Article
- Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.Molecular cancer · 2024Review
- CHIP promotes CAD ubiquitination and degradation to suppress the proliferation and colony formation of glioblastoma cells.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- The Perfect Cup? Coffee-Derived Polyphenols and Their Roles in Mitigating Factors Affecting Type 2 Diabetes Pathogenesis.Molecules (Basel, Switzerland) · 2024Review
- Ubiquitin-proteasome system as a target for anticancer treatment-an update.Archives of pharmacal research · 2023Review
- Unlocking the Potential of Arginine Deprivation Therapy: Recent Breakthroughs and Promising Future for Cancer Treatment.International journal of molecular sciences · 2023Review
- Role of FLCN Phosphorylation in Insulin-Mediated mTORC1 Activation and Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
mTORC1, a central controller of cell proliferation in response to growth factors and nutrients, is dysregulated in cancer. Whereas arginine activates mTORC1, it is overridden by high expression of cytosolic arginine sensor for mTORC1 subunit 1 (CASTOR1). Because cancer cells often encounter low levels of nutrients, an alternative mechanism might exist to regulate CASTOR1 expression. Here we show K29-linked polyubiquitination and degradation of CASTOR1 by E3 ubiquitin ligase RNF167. Furthermore, AKT phosphorylates CASTOR1 at S14, significantly increasing its binding to RNF167, and hence its ubiquitination and degradation, while simultaneously decreasing its affinity to MIOS, leading to mTORC1 activation. Therefore, AKT activates mTORC1 through both TSC2- and CASTOR1-dependent pathways. Several cell types with high CASTOR1 expression are insensitive to arginine regulation. Significantly, AKT and RNF167-mediated CASTOR1 degradation activates mTORC1 independent of arginine and promotes breast cancer progression. These results illustrate a mTORC1 regulating mechanism and identify RNF167 as a therapeutic target for mTORC1-dysregulated diseases.
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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.