Regulation of TFEB and V-ATPases by mTORC1
Regulation of TFEB and V-ATPases by mTORC1
Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) is an important, highly conserved, regulator of cell growth. Ancient among the signals that regulate mTORC1 are nutrients. Amino acids direct mTORC1 to the surface of the late endosome/lysosome, where mTORC1 becomes receptive to other inputs. However, the interplay between endosomes and mTORC1 is poorly understood. Here, we report the discovery of a network that links mTORC1 to a critical component of the late endosome/lysosome, the V-ATPase. In an unbiased screen, we found that mTORC1 regulated the expression of, among other lysosomal genes, the V-ATPases. mTORC1 regulates V-ATPase expression both in cells and in mice. V-ATPase regulation by mTORC1 involves a transcription factor translocated in renal cancer, TFEB. TFEB is required for the expression of a large subset of mTORC1 responsive genes. mTORC1 coordinately regulates TFEB phosphorylation and nuclear localization and in a manner dependent on both TFEB and V-ATPases, mTORC1 promotes endocytosis. These data uncover a regulatory network linking an oncogenic transcription factor that is a master regulator of lysosomal biogenesis, TFEB, to mTORC1 and endocytosis.
- The University of Texas Southwestern Medical Center United States
- Harold C. Simmons Comprehensive Cancer Center United States
- Broad Institute United States
MAP Kinase Signaling System, Amino Acid Motifs, Medizin, Mechanistic Target of Rapamycin Complex 1, Article, Mice, Animals, Phosphorylation, Protein Kinase Inhibitors, Cell Line, Transformed, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Proteins, Fibroblasts, Endocytosis, Protein Transport, Gene Expression Regulation, Enzyme Induction, Multiprotein Complexes, Dactinomycin, Lysosomes, Protein Processing, Post-Translational, Signal Transduction
MAP Kinase Signaling System, Amino Acid Motifs, Medizin, Mechanistic Target of Rapamycin Complex 1, Article, Mice, Animals, Phosphorylation, Protein Kinase Inhibitors, Cell Line, Transformed, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Proteins, Fibroblasts, Endocytosis, Protein Transport, Gene Expression Regulation, Enzyme Induction, Multiprotein Complexes, Dactinomycin, Lysosomes, Protein Processing, Post-Translational, Signal Transduction
27 Research products, page 1 of 3
- 2017IsRelatedTo
- 2018IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2018IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
chevron_left - 1
- 2
- 3
chevron_right
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).412 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
