A sterol-binding protein integrates endosomal lipid metabolism with TOR signaling and nitrogen sensing. Academic Article uri icon


  • 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.

published proceedings

  • Cell

altmetric score

  • 3

author list (cited authors)

  • Mousley, C. J., Yuan, P., Gaur, N. A., Trettin, K. D., Nile, A. H., Deminoff, S. J., ... Bankaitis, V. A.

citation count

  • 76

complete list of authors

  • Mousley, Carl J||Yuan, Peihua||Gaur, Naseem A||Trettin, Kyle D||Nile, Aaron H||Deminoff, Stephen J||Dewar, Brian J||Wolpert, Max||Macdonald, Jeffrey M||Herman, Paul K||Hinnebusch, Alan G||Bankaitis, Vytas A

publication date

  • January 2012

published in