Project/Area Number |
26251021
|
Research Category |
Grant-in-Aid for Scientific Research (A)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Cell biology
|
Research Institution | Institute of Physical and Chemical Research |
Principal Investigator |
Imamoto Naoko 国立研究開発法人理化学研究所, 今本細胞核機能研究室, 主任研究員 (20202145)
|
Co-Investigator(Renkei-kenkyūsha) |
KOSE Shingo 国立研究開発法人理化学研究所, 今本細胞核機能研究室, 専任研究員 (90333278)
MAMADA Hiroshi 国立研究開発法人理化学研究所, 今本細胞核機能研究室, 特別研究員 (90568734)
|
Research Collaborator |
TAKAGI Masatoshi 国立研究開発法人理化学研究所, 今本細胞核機能研究室, 専任研究員
KIMURA Makato 国立研究開発法人理化学研究所, 今本細胞核機能研究室, 専任研究員
OGAWA Yutaka 国立研究開発法人理化学研究所, 今本細胞核機能研究室, 研究員
LEE Soo Jae Chungbuk National University, College of Pharmacy, Professor
EPELEG Orly Hebrew University Medical Center, Professor
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥40,690,000 (Direct Cost: ¥31,300,000、Indirect Cost: ¥9,390,000)
Fiscal Year 2016: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2015: ¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
Fiscal Year 2014: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000)
|
Keywords | 核-細胞質間輸送 / 熱ストレス / 分子シャペロンHsp70 / Hikeshi / HSF1 / タンパク質毒性ストレス / タンパク質恒常性 / 核ー細胞質間輸送 / 熱ショックストレス / 神経遺伝性疾患 / 蛍光相互相関法 / グルコース飢餓 / ノックアウトマウス |
Outline of Final Research Achievements |
Stresses significantly affect nuclear transport systems. Many of the well-characterized Importin nuclear transport pathways that are active under normal conditions are down regulated in response to stress.Under such stress condition, a nuclear transport carrier named Hikeshi drives nuclear import of molecular chaperone Hsp70. Hikeshi is an evolutionarily conserved protein, and its function has not been previously characterized. We analyzed Hikeshi homologues from several organisms and found biochemical nature of Hikeshi homologues is conserved. Hikeshi is not an essential protein in lower eukaryotes although it affects stress sensitivity. However, dysfunction of Hikeshi has lethal effects in higher eukaryotes. Our analysis reveals that Hikeshi is involved in a regulation of HSF1, not only under stress condition but also under normal condition. We suggest Hikeshi is crucial for the maintenance of proteostasis at basal level in cells, which affect variety of organismal function.
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