Project/Area Number |
16207013
|
Research Category |
Grant-in-Aid for Scientific Research (A)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Cell biology
|
Research Institution | Kyoto University |
Principal Investigator |
NAGATA Kazuhiro Kyoto University, Institute for Frontier Medical Sciences, Prof., 再生医科学研究所, 教授 (50127114)
|
Co-Investigator(Kenkyū-buntansha) |
HOSOKAWA Nobuko Kyoto University, Institute for Frontier Medical Sciences, Assoc. Professor, 再生医科学研究所, 助教授 (00263153)
|
Project Period (FY) |
2004 – 2006
|
Project Status |
Completed (Fiscal Year 2006)
|
Budget Amount *help |
¥50,180,000 (Direct Cost: ¥38,600,000、Indirect Cost: ¥11,580,000)
Fiscal Year 2006: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000)
Fiscal Year 2005: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000)
Fiscal Year 2004: ¥20,800,000 (Direct Cost: ¥16,000,000、Indirect Cost: ¥4,800,000)
|
Keywords | Molecular Chaperone / Quality control / ER associated degradation / EDEM |
Research Abstract |
We found and cloned the gene of a novel stress protein HSP47 which resides in the endoplasmic reticulum (ER) acting as a collagen-specific molecular chaperone in the pathway of collagen biosynthesis, processing and secretion. In addition to the binding specificity to collagen, the expression of HSP47 is always closely correlated with those of collagens during the normal development of mouse embryo as well as in the pathophysiological conditions including liver and renal fibrosis. We are also working on the intracellular mechanism of ERQC (ER quality control) including ERAD (ER associated degradation). We have cloned a mouse gene EDEM, and EDEM family proteins, which are involved in the ERAD of glycoproteins. Furthermore, we also identified and cloned ERdj5 as EDEM-binding J-domain-containing chaperone-like protein in the ER, which we showed is involved in ERAD as a novel reductase in the ER. We are also studying cytosolic chaperonin CCT and showed that CCT prevents the aggregation of poly-glutamine containing proteins. This finding is directly related to the development of therapeutic strategy for neurodegenerative diseases.
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