A sterol-binding protein integrates endosomal lipid metabolism with TOR signaling and nitrogen sensing
MetadataShow full item record
Kes1, and other oxysterol-binding protein superfamily members, are involved in membrane and lipid trafficking through trans-Golgi network (TGN) and endosomal systems. We demonstrate that Kes1 represents a sterol-regulated antagonist of TGN/endosomal phosphatidylinositol-4-phosphate signaling. This regulation modulates TOR activation by amino acids and dampens gene expression driven by Gcn4, the primary transcriptional activator of the general amino acid control regulon. Kes1-mediated repression of Gcn4 transcription factor activity is characterized by nonproductive Gcn4 binding to its target sequences, involves TGN/endosome-derived sphingolipid signaling, and requires activity of the cyclin-dependent kinase 8 (CDK8) module of the enigmatic “large Mediator” complex. These data describe a pathway by which Kes1 integrates lipid metabolism with TORC1 signaling and nitrogen sensing.
Showing items related by title, author, creator and subject.
Trans-Golgi network and endosome dynamics connect ceramide homeostasis with regulation of the unfolded protein response and TOR signaling in yeastMousley, Carl; Tyeryar, K.; Ile, K.; Schaaf, G.; Brost, R.; Boone, C.; Guan, X.; Wenk, M.; Bankaitis, V. (2008)Synthetic genetic array analyses identify powerful genetic interactions between a thermosensitive allele (sec14-1 ts)ofthe structural gene for the major yeast phosphatidylinositol transfer protein (SEC14) and a structural ...
PI3K-C2γ is a Rab5 effector selectively controlling endosomal Akt2 activation downstream of insulin signallingBraccini, L.; Ciraolo, E.; Campa, C.; Perino, A.; Longo, D.; Tibolla, G.; Pregnolato, M.; Cao, Y.; Tassone, B.; Damilano, F.; Laffargue, M.; Calautti, E.; Falasca, Marco; Norata, G.; Backer, J.; Hirsch, E. (2015)In the liver, insulin-mediated activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is at the core of metabolic control. Multiple PI3K and Akt isoenzymes are found in hepatocytes and whether isoform-selective ...
A Lipid Transfer Protein Signaling Axis Exerts Dual Control of Cell-Cycle and Membrane Trafficking SystemsHuang, J.; Mousley, Carl; Dacquay, L.; Maitra, N.; Drin, G.; He, C.; Ridgway, N.; Tripathi, A.; Kennedy, M.; Kennedy, B.; Liu, W.; Baetz, K.; Polymenis, M.; Bankaitis, V. (2018)© 2017 Elsevier Inc. Kes1/Osh4 is a member of the conserved, but functionally enigmatic, oxysterol binding protein-related protein (ORP) superfamily that inhibits phosphatidylinositol transfer protein (Sec14)-dependent ...