ArticleHuman molecular genetics2018
The TMEM127 human tumor suppressor is a component of the mTORC1 lysosomal nutrient-sensing complex.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Structural insights into predicted protein-protein interactions and protein complexes in the human proteome.Scientific reports · 2026Article
- [Germline mutations define the prognosis and therapy of pheochromocytomas and paragangliomas].Magyar onkologia · 2025Review
- Combining WGCNA and machine learning to identify mechanisms and biomarkers of hyperthyroidism and atrial fibrillation.Frontiers in cardiovascular medicine · 2025Article
- The Molecular Classification of Pheochromocytomas and Paragangliomas: Discovering the Genomic and Immune Landscape of Metastatic Disease.Endocrine pathology · 2024Review
- Childhood Multiple Endocrine Neoplasia (MEN) Syndromes: Genetics, Clinical Heterogeneity and Modifying Genes.Journal of clinical medicine · 2024Review
- Loss of tumor suppressor TMEM127 drives RET-mediated transformation through disrupted membrane dynamics.eLife · 2024Article
- Loss of Tumour Suppressor TMEM127 Drives RET-mediated Transformation Through Disrupted Membrane Dynamics.bioRxiv : the preprint server for biology · 2024Article
- Computational analysis of protein-protein interactions of cancer drivers in renal cell carcinoma.FEBS open bio · 2024Article
- TMEM127 suppresses tumor development by promoting RET ubiquitination, positioning, and degradation.Cell reports · 2023Article
- The Ragulator complex: delving its multifunctional impact on metabolism and beyond.Inflammation and regeneration · 2023Review
- Genetics of Pheochromocytomas and Paragangliomas Determine the Therapeutical Approach.International journal of molecular sciences · 2022Review
- San Antonio Nathan Shock Center: your one-stop shop for aging research.GeroScience · 2021Article
- Insights into Mechanisms of Pheochromocytomas and Paragangliomas Driven by Known or New Genetic Drivers.Cancers · 2021Review
- Genotype-Phenotype Features of Germline Variants of the TMEM127 Pheochromocytoma Susceptibility Gene: A 10-Year Update.The Journal of clinical endocrinology and metabolism · 2021Article
- Functional Characterization of TMEM127 Variants Reveals Novel Insights into Its Membrane Topology and Trafficking.The Journal of clinical endocrinology and metabolism · 2020Article
- The Tumour Suppressor TMEM127 Is a Nedd4-Family E3 Ligase Adaptor Required by Salmonella SteD to Ubiquitinate and Degrade MHC Class II Molecules.Cell host & microbe · 2020Article
- Identification of a TMEM127 variant in a patient with paraganglioma and acromegaly.Endocrinology, diabetes & metabolism case reports · 2020Article
- The tumor suppressor TMEM127 regulates insulin sensitivity in a tissue-specific manner.Nature communications · 2019Article
- Signal integration in the (m)TORC1 growth pathway.Frontiers in biology · 2018Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The TMEM127 tumor suppressor gene encodes a transmembrane protein of unknown function mutated in pheochromocytomas and, rarely, in renal cancers. Tumors with inactivating TMEM127 mutations have increased mTORC1 signaling by undefined mechanisms. Here we report that TMEM127 interacts with the lysosome-anchored complex comprised of Rag GTPases, the LAMTOR pentamer (or 'ragulator') and vATPase, which controls amino acid-mediated mTORC1 activation. We found that under nutrient-rich conditions TMEM127 expression reduces mTORC1 recruitment to Rags. In addition, TMEM127 interacts with LAMTOR in an amino acid-dependent manner and decreases the LAMTOR1-vATPase association, while TMEM127-vATPase binding requires intact lysosomal acidification but is amino acid independent. Conversely, both murine and human cells lacking TMEM127 accumulate LAMTOR proteins in the lysosome. Consistent with these findings, pheochromocytomas with TMEM127 mutations have increased levels of LAMTOR proteins. These results suggest that TMEM127 interactions with ragulator and vATPase at the lysosome contribute to restrain mTORC1 signaling in response to amino acids, thus explaining the increased mTORC1 activation seen in TMEM127-deficient tumors.
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Registered trials
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