Project/Area Number |
09276103
|
Research Category |
Grant-in-Aid for Scientific Research on Priority Areas (A)
|
Allocation Type | Single-year Grants |
Research Institution | Kyoto University |
Principal Investigator |
MORI Masataka Kumamoto University, School of Medicine, Professor, 医学部, 教授 (40009650)
|
Co-Investigator(Kenkyū-buntansha) |
MIHARA Katsuyoshi Kyushu University, Graduate School of Medical Science, Professor, 大学院・医学系研究科, 教授 (40029963)
ITO Koreaki Kyoto University, Institute for Virus Research, Professor, ウイルス研究所, 教授 (90027334)
NAGATA Kazuhiro Kyoto University, Institute for Medical Science , Professor, 再生医科学研究所, 教授 (50127114)
HIGUCHI Keiichi Sinshu University, Medical School, Professor, 医学部, 教授 (20173156)
ENDO Toshiya Nagoya University, Graduate School of Science, Professor, 大学院・理学研究科, 教授 (70152014)
梅園 和彦 京都大学, ウイルス研究所, 教授 (50183752)
中野 明彦 理化学研究所, 主任研究員 (90142140)
|
Project Period (FY) |
1997 – 2001
|
Project Status |
Completed (Fiscal Year 2001)
|
Budget Amount *help |
¥339,000,000 (Direct Cost: ¥339,000,000)
Fiscal Year 2000: ¥79,000,000 (Direct Cost: ¥79,000,000)
Fiscal Year 1999: ¥81,000,000 (Direct Cost: ¥81,000,000)
Fiscal Year 1998: ¥73,000,000 (Direct Cost: ¥73,000,000)
Fiscal Year 1997: ¥106,000,000 (Direct Cost: ¥106,000,000)
|
Keywords | molecular chaperone / heat shock protein / folding / mitochondria import / secretory protein / amyloidosis / UPR / ミトコンドリア / 小胞体 / 葉緑体 / 膜透過 / 折り畳み / 品質管理 / アミロイド / タンパク質の細胞内輸送 / Hsp70 / DnaJホモログ / カルネキシン / Hsp47 / アミロイド形成 / hsp70 / 小胞輸送 / hsp47 |
Research Abstract |
Cytosolic hsp70-dj1/dj2 chaperone system was found to prevent NO-induced apoptosis in macrophages. Knockout mice for the HSP47 gene were generated and characterized. Many mutants of SecA were isolated and their interaction with SecY was studied. A cytosolic factor which induces cytochrome c release depending on staurosporin and dATP, was purified and found to be 20S proteasome. Chaperone activity of mitochondrial hsp70 was analyzed using denatured luciferase as a substrate. Exogenously added amyloid fibers were found to induce fiber formation of endogenous amyloid proteins. Oxidation of thiol of newly-synthesized proteins was shown to occur through S-S shuffling with glutathione and cysteine. Adjucent molecule of FtsH, an AAA ATPase, was shown to be important for ATP hydrolysis. Haclp, a transcription factor involved in unfolded protein response (UPR) in yeast, was shown to be induced when its mRNA undergoes stress-specific splicing.
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