Inactivation of Mammalian Target of Rapamycin Increases STAT1 Nuclear Content and Transcriptional Activity in α4- and Protein Phosphatase 2A-dependent Fashion
| Autor: | Arnold S. Kristof, Shuo Xing, Jill A. Fielhaber, Jason Tan, Catherine M. Biggs, Ying Shan Han, Kwang-bo Joung |
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| Rok vydání: | 2009 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Apoptosis Saccharomyces cerevisiae Biology Biochemistry mTORC2 Cell Line Humans Protein Phosphatase 2 STAT1 Molecular Biology Transcription factor Protein kinase B PI3K/AKT/mTOR pathway Adaptor Proteins Signal Transducing Cell Nucleus TOR Serine-Threonine Kinases Mechanisms of Signal Transduction RPTOR Intracellular Signaling Peptides and Proteins Ribosomal Protein S6 Kinases 70-kDa Cell Biology Protein phosphatase 2 Cell biology STAT1 Transcription Factor Gene Expression Regulation Multiprotein Complexes biology.protein Protein Kinases Proto-Oncogene Proteins c-akt Molecular Chaperones |
| Zdroj: | Journal of Biological Chemistry. 284:24341-24353 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m109.033530 |
| Popis: | Target of rapamycin (TOR) is a highly conserved serine/threonine kinase that controls cell growth, primarily via regulation of protein synthesis. In Saccharomyces cerevisiae, TOR can also suppress the transcription of stress response genes by a mechanism involving Tap42, a serine/threonine phosphatase subunit, and the transcription factor Msn2. A physical association between mammalian TOR (mTOR) and the transcription factor signal transducer and activator of transcription-1 (STAT1) was recently identified in human cells, suggesting a similar role for mTOR in the transcription of interferon-gamma-stimulated genes. In the current study, we identified a macromolecular protein complex composed of mTOR, STAT1, the Tap42 homologue alpha4, and the protein phosphatase 2A catalytic subunit (PP2Ac). Inactivation of mTOR enhanced its association with STAT1 and increased STAT1 nuclear content in PP2Ac-dependent fashion. Depletion of alpha4, PP2A, or mTOR enhanced the induction of early (i.e. IRF-1) and late (i.e. caspase-1, hiNOS, and Fas) STAT1-dependent genes. The regulation of IRF-1 or caspase-1 by mTOR was independent of other known mTOR effectors p70 S6 kinase and Akt. These results describe a new role for mTOR and alpha4/PP2A in the control of STAT1 nuclear content, and the expression of interferon-gamma-sensitive genes involved in immunity and apoptosis. |
| Databáze: | OpenAIRE |
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