Sensing mechanism of IRE1 to abnormal proteins
| Project/Area Number |
14580699
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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 |
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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| 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)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | ER stress / IRE1 / GRP78 / BiP / Kar2 / Unfolded protein response / 小胞体 / ストレス応答 / センシング |
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| Research Abstract |
The luminal domain of the Type I transmembrane protein Ire1 senses endoplasmic reticulum(ER) stress by undefined mechanism to upregulate the signaling pathway for the unfolded protein response. We previously reported that under nonstressed conditions, the ER chaperone GRP78/BiP binds and represses Ire1. But it is still unclear how this event contributes to the overall regulation of Ire1.
In this Ire1 mutation study revealed that luminal domain of Ire1 was consisted of 5 subregions, termed subregions I to V sequentially from the N-terminus. Ire1 lost activity when internal deletions of subregion II and IV were made. This suggests that subregions II and IV were prerequisite for the activation of Ire1, while BiP-binding site resides in subregion V. Although deletion of BiP-binding site rendered Ire1 unaltered ER stress inductivity hypersensitivity ethanol and high temperature were observed. Therefore we concluded that BiP is not the principal determinant of Ire1 activity but adjuster for sensitivity to various stresses in the ER stress-sensory system.
Next, we analyzed the essential subregions, II and IV for Ire1 activity. Recombinant proteins of subregion II to IV formed homodimers, but this dimmer formation was impaired by an internal deletion of subregion IV. Furthermore, recombinant fragments of subregion IV exhibited a self-binding ability. Therefore, subregion IV plays an essential role to promote Ire1 dimer formation.
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Report
(4 results)
Research Products
(5 results)
