| Project/Area Number |
15570160
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Nara Institute of Science and Technology |
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Principal Investigator |
KIMATA Yukio Nara Institute of Science and Technology, Research and Education Center for Genetic Information, Assistant professor, 遺伝子教育研究センター, 助手 (60263448)
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| Co-Investigator(Kenkyū-buntansha) |
KOHNO Kenji Nara Institute of Science and Technology, Research and Education Center for Genetic Information, Professor, 遺伝子教育研究センター, 教授 (50142005)
TSURU Akio Nara Institute of Science and Technology, Research and Education Center for Genetic Information, Assistant professor, 遺伝子教育研究センター, 助手 (80273861)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Stress / ER / molecular chaperon / stress response / UPR / RNA / splicing / シャペロン / 小胞体ストレス / ストレス対応 |
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| Research Abstract |
An endoplasmic reticulum (ER)-located transmembrane protein Ire1 is a site-specific RNase that is activated in response to ER stress. Splicing of mRNAs encoding Hac1 and XBP1 by Ire1 results in production of mature transcription factors that induce various genes including those of ER chaperons. In addition, Ire1β, one of two mammalian Ire1 variants, cleaves 28S rRNA to attenuate translation. Our work has focused on understanding how unfolded proteins in the endoplasmic reticulum are recognized by Ire1. We previously reported that under nonstressed conditions, the ER chaperone BiP binds and represses Ire1. It is still unclear how this event contributes to the overall regulation of Ire1. The present yeast Ire1 mutation study shows that the luminal domain possesses two subregions that seem indispensable for activity. The BiP-binding site was assigned not to these subregions, but to a region neighboring the transmembrane domain. Phenotypic comparison of several Ire1 mutants carrying deletions in the indispensable subregions suggests these subregions are responsible for multiple events that are prerequisites for activation of the overall Ire1 proteins. Unexpectedly, deletion of the BiP-binding site rendered Ire1 unaltered in ER stress inducibility, but hypersensitive to ethanol and high temperature. We conclude that in the ER stress-sensory system, BiP is not the principal determinant of Ire1 activity, but an adjustor for sensitivity to various stresses.
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