A sterol-binding protein integrates endosomal lipid metabolism with TOR signaling and nitrogen sensing
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 r...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal Article |
| Published: |
2012
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| Online Access: | http://hdl.handle.net/20.500.11937/16747 |
| _version_ | 1848749264705945600 |
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| author | Mousley, Carl Yuan, P. Gaur, N. Trettin, K. Nile, A. Deminoff, S. Dewar, B. Wolpert, M. MacDonald, J. Herman, P. Hinnebusch, A. Bankaitis, V. |
| author_facet | Mousley, Carl Yuan, P. Gaur, N. Trettin, K. Nile, A. Deminoff, S. Dewar, B. Wolpert, M. MacDonald, J. Herman, P. Hinnebusch, A. Bankaitis, V. |
| author_sort | Mousley, Carl |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T07:18:11Z |
| format | Journal Article |
| id | curtin-20.500.11937-16747 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:18:11Z |
| publishDate | 2012 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-167472017-09-13T15:44:54Z A sterol-binding protein integrates endosomal lipid metabolism with TOR signaling and nitrogen sensing Mousley, Carl Yuan, P. Gaur, N. Trettin, K. Nile, A. Deminoff, S. Dewar, B. Wolpert, M. MacDonald, J. Herman, P. Hinnebusch, A. Bankaitis, V. 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. 2012 Journal Article http://hdl.handle.net/20.500.11937/16747 10.1016/j.cell.2011.12.026 unknown |
| spellingShingle | Mousley, Carl Yuan, P. Gaur, N. Trettin, K. Nile, A. Deminoff, S. Dewar, B. Wolpert, M. MacDonald, J. Herman, P. Hinnebusch, A. Bankaitis, V. A sterol-binding protein integrates endosomal lipid metabolism with TOR signaling and nitrogen sensing |
| title | A sterol-binding protein integrates endosomal lipid metabolism with TOR signaling and nitrogen sensing |
| title_full | A sterol-binding protein integrates endosomal lipid metabolism with TOR signaling and nitrogen sensing |
| title_fullStr | A sterol-binding protein integrates endosomal lipid metabolism with TOR signaling and nitrogen sensing |
| title_full_unstemmed | A sterol-binding protein integrates endosomal lipid metabolism with TOR signaling and nitrogen sensing |
| title_short | A sterol-binding protein integrates endosomal lipid metabolism with TOR signaling and nitrogen sensing |
| title_sort | sterol-binding protein integrates endosomal lipid metabolism with tor signaling and nitrogen sensing |
| url | http://hdl.handle.net/20.500.11937/16747 |