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TFEB at a glance

Journal of Cell Science · 2016 · Vol. 129(13) · pp. 2475–2481
Gennaro NapolitanoAndrea Ballabio

Abstract

The transcription factor EB (TFEB) plays a pivotal role in the regulation of basic cellular processes, such as lysosomal biogenesis and autophagy. The subcellular localization and activity of TFEB are regulated by mechanistic target of rapamycin (mTOR)-mediated phosphorylation, which occurs at the lysosomal surface. Phosphorylated TFEB is retained in the cytoplasm, whereas dephosphorylated TFEB translocates to the nucleus to induce the transcription of target genes. Thus, a lysosome-to-nucleus signaling pathway regulates cellular energy metabolism through TFEB. Recently, in vivo studies have revealed that TFEB is also involved in physiological processes, such as lipid catabolism. TFEB has attracted a lot of attention owing to its ability to induce the intracellular clearance of pathogenic factors in a variety of murine models of disease, such as Parkinson's and Alzheimer's, suggesting that novel therapeutic strategies could be based on the modulation of TFEB activity. In this Cell Science at a Glance article and accompanying poster, we present an overview of the latest research on TFEB function and its implication in human diseases.

Autophagy in Disease and TherapyCellular transport and secretionPlant Molecular Biology ResearchTFEBAutophagyBiologyBasic helix-loop-helix leucine zipper transcription factorsCell biologyLysosomeTranscription factorMechanistic target of rapamycinBiogenesisPI3K/AKT/mTOR pathway

MeSH terms

Alzheimer DiseaseAutophagyCell NucleusEnergy MetabolismHumansLysosomesMetabolismParkinson DiseaseSignal TransductionLipid MetabolismBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsTOR Serine-Threonine Kinases

Funding

  • Cancer Research Institute
  • Beyond Batten Disease Foundation
  • European Commission
  • Fondazione Telethon
  • Associazione Italiana per la Ricerca sul Cancro
  • Fondazione Italiana per la Ricerca sul Cancro
  • National Institutes of Health
  • European Research Council
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