| Literature DB >> 22341443 |
Carl J Mousley1, Peihua Yuan, Naseem A Gaur, Kyle D Trettin, Aaron H Nile, Stephen J Deminoff, Brian J Dewar, Max Wolpert, Jeffrey M Macdonald, Paul K Herman, Alan G Hinnebusch, Vytas A Bankaitis.
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. Copyright ÂEntities:
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Year: 2012 PMID： 22341443 PMCID： PMC3285437 DOI： 10.1016/j.cell.2011.12.026
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582