Gene interactions and pathways from curated databases and text-mining
EMBO J 2011, PMID: 21804531

Regulation of TFEB and V-ATPases by mTORC1.

Peña-Llopis, Samuel; Vega-Rubin-de-Celis, Silvia; Schwartz, Jacob C; Wolff, Nicholas C; Tran, Tram Anh T; Zou, Lihua; Xie, Xian-Jin; Corey, David R; Brugarolas, James

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.

Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System
Document information provided by NCBI PubMed

Text Mining Data

TFEB — mTORC1: " Regulation of TFEB and V-ATPases by mTORC1 "

V-ATPase → mTORC1: " mTORC1 regulates V-ATPase expression both in cells and in mice "

V-ATPase → transcription factor: " V-ATPase regulation by mTORC1 involves a transcription factor translocated in renal cancer, TFEB "

V-ATPase — mTORC1: " V-ATPase regulation by mTORC1 involves a transcription factor translocated in renal cancer, TFEB "

TFEB → mTORC1: " mTORC1 coordinately regulates TFEB phosphorylation and nuclear localization and in a manner dependent on both TFEB and V-ATPases, mTORC1 promotes endocytosis "

Manually curated Databases

No curated data.