Open AccessA Sterol-Binding Protein Integrates Endosomal Lipid Metabolism with TOR Signaling and Nitrogen Sensing
Author(s) -
Carl J. Mousley,
Peihua Yuan,
Naseem A. Gaur,
Kyle Trettin,
Aaron H. Nile,
Stephen J. Deminoff,
Brian J. Dewar,
Max Wolpert,
Jeffrey M. Macdonald,
Paul K. Herman,
Alan G. Hinnebusch,
Vytas A. Bankaitis
Publication year - 2012
Publication title -
cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 26.304
H-Index - 776
eISSN - 1097-4172
pISSN - 0092-8674
DOI - 10.1016/j.cell.2011.12.026
Subject(s) - biology , endosome , lipid metabolism , sterol , sterol regulatory element binding protein , microbiology and biotechnology , signal transduction , biochemistry , cholesterol , receptor
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.
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