ArticleCell reports2023
TMEM127 suppresses tumor development by promoting RET ubiquitination, positioning, and degradation.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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.
The trial behind it
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
10 citing papers in PubMed, 20 citations in OpenAlex.
- Effects of Food on the Pharmacokinetics and Safety of HA121-28 Tablet, a Novel Multi-Targeting Tyrosine Kinase Inhibitor, in Healthy Chinese Subjects: A Phase I Clinical Trial.Drug design, development and therapy · 2025Trial
- Identifying TMEM127-deficient pheochromocytomas/paragangliomas via RET overexpression by immunohistochemistry.Research square · 2026Article
- α-Ketoglutarate promotes amino acid depletion and suppresses B-cell lymphoma growth and development.Blood · 2025Article
- Article
- Combining WGCNA and machine learning to identify mechanisms and biomarkers of hyperthyroidism and atrial fibrillation.Frontiers in cardiovascular medicine · 2025Article
- Mapping the cancer surface proteome in search of target antigens for immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Genetic and Molecular Biomarkers in Aggressive Pheochromocytomas and Paragangliomas.International journal of molecular sciences · 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
- Review
Corrections and comments
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Authors and funding
21 authors at 2 institutions in 2 countries.
Funding
Abstract
The TMEM127 gene encodes a transmembrane protein of poorly known function that is mutated in pheochromocytomas, neural crest-derived tumors of adrenomedullary cells. Here, we report that, at single-nucleus resolution, TMEM127-mutant tumors share precursor cells and transcription regulatory elements with pheochromocytomas carrying mutations of the tyrosine kinase receptor RET. Additionally, TMEM127-mutant pheochromocytomas, human cells, and mouse knockout models of TMEM127 accumulate RET and increase its signaling. TMEM127 contributes to RET cellular positioning, trafficking, and lysosome-mediated degradation. Mechanistically, TMEM127 binds to RET and recruits the NEDD4 E3 ubiquitin ligase for RET ubiquitination and degradation via TMEM127 C-terminal PxxY motifs. Lastly, increased cell proliferation and tumor burden after TMEM127 loss can be reversed by selective RET inhibitors in vitro and in vivo. Our results define TMEM127 as a component of the ubiquitin system and identify aberrant RET stabilization as a likely mechanism through which TMEM127 loss-of-function mutations cause pheochromocytoma.
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What OpenQuestion holds
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.