ArticleMolecular biology of the cell2022
PP2A-dependent TFEB activation is blocked by PIKfyve-induced mTORC1 activity.
Article in Molecular biology of the cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 36 citations in OpenAlex.
- Substrate-specific regulation of the mTORC1 pathway by G protein-coupled receptors.The Biochemical journal · 2026Article
- Targeting PIKfyve: Chemical Biology and Drug Discovery Insights.Chemical biology & drug design · 2026Review
- Lysosomes and lysosomal dysfunction in ageing biology.Nature cell biology · 2026Review
- PIKfyve preserves endolysosomal function in photoreceptors and RPE cells to maintain retinal integrity.Cell death & disease · 2026Article
- Article
- Artificial intelligence revolutionizing CNS drug discovery and development.Drug discovery today · 2026Review
- Disruption of the PIKfyve complex unveils an adaptive mechanism to promote lysosomal repair and mitochondrial homeostasis.Nature communications · 2025Article
- Integrative analysis based on CRISPR screen identifies apilimod as a potential therapeutic agent for cisplatin-induced acute kidney injury treatment.Science China. Life sciences · 2025Article
- An AMBRA1, ULK1 and PP2A regulatory network regulates cytotoxic T cell differentiation via TFEB activation.Scientific reports · 2024Article
- Coronary Microvascular Dysfunction Is Associated With Augmented Lysosomal Signaling in Hypercholesterolemic Mice.Journal of the American Heart Association · 2024Article
- Article
- mTORC1 signaling and diabetic kidney disease.Diabetology international · 2024Review
- A PIKfyve modulator combined with an integrated stress response inhibitor to treat lysosomal storage diseases.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Pressure sensing of lysosomes enables control of TFEB responses in macrophages.Nature cell biology · 2024Article
- Coronary Microvascular Dysfunction is Associated with Augmented Lysosomal Signaling in Hypercholesterolemic Mice.bioRxiv : the preprint server for biology · 2024Article
- Review
- Mitf, with Yki and STRIPAK-PP2A, is a key determinant of form and fate in the progenitor epithelium of the Drosophila eye.European journal of cell biology · 2024Article
- Article
- Stress-induced microautophagy is coordinated with lysosome biogenesis and regulated by PIKfyve.Molecular biology of the cell · 2024Article
- Predictive, preventive, and personalized medicine in breast cancer: targeting the PI3K pathway.Journal of translational medicine · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Transcriptional factor EB (TFEB) is a master regulator of genes required for autophagy and lysosomal function. The nuclear localization of TFEB is blocked by the mechanistic target of rapamycin complex 1 (mTORC1)-dependent phosphorylation of TFEB at multiple sites including Ser-211. Here we show that inhibition of PIKfyve, which produces phosphatidylinositol 3,5-bisphosphate on endosomes and lysosomes, causes a loss of Ser-211 phosphorylation and concomitant nuclear localization of TFEB. We found that while mTORC1 activity toward S6K1, as well as other major mTORC1 substrates, is not impaired, PIKfyve inhibition specifically impedes the interaction of TFEB with mTORC1. This suggests that mTORC1 activity on TFEB is selectively inhibited due to loss of mTORC1 access to TFEB. In addition, we found that TFEB activation during inhibition of PIKfyve relies on the ability of protein phosphatase 2A (PP2A) but not calcineurin/PPP3 to dephosphorylate TFEB Ser-211. Thus when PIKfyve is inhibited, PP2A is dominant over mTORC1 for control of TFEB phosphorylation at Ser-S211. Together these findings suggest that mTORC1 and PP2A have opposing roles on TFEB via phosphorylation and dephosphorylation of Ser-211, respectively, and further that PIKfyve inhibits TFEB activity by facilitating mTORC1-dependent phosphorylation of TFEB.
Indexed as
Identifiers
What Socratic 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 Socratic graph.