2006 Fiscal Year Final Research Report Summary
Molecular mechanism of ER-related degradation
| Project/Area Number |
14037230
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kyoto University |
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Principal Investigator |
NAGATA Kazuhiro Kyoto University, Institute for Medical Sciences, Professor (50127114)
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| Co-Investigator(Kenkyū-buntansha) |
HOSOKAWA Nobuko Kyoto University, Institute for Frontier Medical Sciences, Assoc. Professor (00263153)
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| Project Period (FY) |
2002 – 2006
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| Keywords | Molecular Chaperone / Quality control / ER associated degradation / EDEM |
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| Research Abstract |
We have got several important new findings during this period on the quality control mechanism of misfolded proteins in the endoplasmic reticulum. First, we identified EDEM as a novel component for the recognition of misfolded proteins that are to be degraded through ER-associated degradation (ERAD) system: EDEM recognizes mannose 8 form of N-glycans on the misfolded proteins and facilitates the ERAD. On the other hand, we also figured out the mechanism on the inhibition of aggregate formation of poly-glutamine repeat proteins such as Huntingtin by cytosolic chaperonin CCT. CCT inhibited the oligomer formation of polyQ proteins resulting in inhibiting the aggregation. We also identified the sequence that can be recognized by CCT on the beta-sheet containing proteins for the productive folding. Hsp47, a collagen-specific molecular chaperone that we found in 1986, was newly found to be essential for fibril formation by collagen secreted into the extracellular matrix. Without Hsp47, secreted collagen failed to make thick collagen bundles, which suggested Hsp47 is a promising therapeutic target for various fibrotic diseases including liver cirrhosis.
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Research Products
(86 results)
