Author/Authors :
Carl J. Mousley، نويسنده , , Peihua Yuan، نويسنده , , Naseem A. Gaur، نويسنده , , Kyle D. Trettin، نويسنده , , Aaron H. Nile، نويسنده , , Stephen J. Deminoff، نويسنده , , Brian J. Dewar، نويسنده , , Max Wolpert، نويسنده , , Jeffrey M. Macdonald، نويسنده , , Paul K. Herman، نويسنده , , Alan G. Hinnebusch، نويسنده , , Vytas A. Bankaitis، نويسنده ,
Abstract :
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.
