ArticleCell research2024
The rapid proximity labeling system PhastID identifies ATP6AP1 as an unconventional GEF for Rheb.
Article in Cell research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 19 citations in OpenAlex.
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- Proximal Proteomics Reveals Potential Regulators of Programmed Death-Ligand 1 in Human Cancer.ACS omega · 2026Article
- Proteomic investigation of signaling dynamics: from static maps to network rewiring.Bioscience reports · 2026Review
- Controlling distance, time and reactivity: Chemical principles of proximity labeling.Current opinion in chemical biology · 2026Review
- Proteomic Characterization of AS1411 Reveals ATP6AP1 as a Mediator of Triple-Negative Breast Cancer Progression.Proteomics · 2026Article
- Integrative proteomic characterization of human lung adenocarcinoma with KRAS G12 mutations reveals molecular pathogenesis.Journal of advanced research · 2026Article
- The dynamic and heterogeneous composition of biomolecular condensates and its functional relevance.Nature reviews. Molecular cell biology · 2026Review
- Histidine phosphorylation of NME1 regulates the Hippo pathway via the ARHGAP17-CDC42-cytoskeleton axis.Life medicine · 2026Article
- UCK2 Drives Lung Adenocarcinoma Progression and Immune Dysregulation via the RHEB/mTOR Signaling Axis.Oncology research · 2026Article
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Proximal proteomics reveals a landscape of human nuclear condensates.Nature cell biology · 2025Article
- Disruption of ZC3H15 compromises telomere length maintenance by entrapping telomerase within cajal bodies.Cell & bioscience · 2025Article
- V-ATPase and Lysosomal Energy Sensing in Periodontitis and Medicine-Related Osteonecrosis of the Jaw.Biomolecules · 2025Review
- Evolution of growth factor signaling to the TSC complex to regulate mTORC1.Science signaling · 2025Review
- Lysosomal EGFR acts as a Rheb-GEF independent of its kinase activity to activate mTORC1.Cell research · 2025Article
- Lysosomal EGFR functions as a GEF for Rheb.Cell research · 2025Article
- New insights into tuberous sclerosis complex: from structure to pathogenesis.Frontiers in cell and developmental biology · 2025Review
- Making PI3K superfamily enzymes run faster.Advances in biological regulation · 2025Review
- ER-phagy restrains inflammatory responses through its receptor UBAC2.The EMBO journal · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
Rheb is a small G protein that functions as the direct activator of the mechanistic target of rapamycin complex 1 (mTORC1) to coordinate signaling cascades in response to nutrients and growth factors. Despite extensive studies, the guanine nucleotide exchange factor (GEF) that directly activates Rheb remains unclear, at least in part due to the dynamic and transient nature of protein-protein interactions (PPIs) that are the hallmarks of signal transduction. Here, we report the development of a rapid and robust proximity labeling system named Pyrococcus horikoshii biotin protein ligase (PhBPL)-assisted biotin identification (PhastID) and detail the insulin-stimulated changes in Rheb-proximity protein networks that were identified using PhastID. In particular, we found that the lysosomal V-ATPase subunit ATP6AP1 could dynamically interact with Rheb. ATP6AP1 could directly bind to Rheb through its last 12 amino acids and utilizes a tri-aspartate motif in its highly conserved C-tail to enhance Rheb GTP loading. In fact, targeting the ATP6AP1 C-tail could block Rheb activation and inhibit cancer cell proliferation and migration. Our findings highlight the versatility of PhastID in mapping transient PPIs in live cells, reveal ATP6AP1's role as an unconventional GEF for Rheb, and underscore the importance of ATP6AP1 in integrating mTORC1 activation signals through Rheb, filling in the missing link in Rheb/mTORC1 activation.
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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.