| Project/Area Number |
63304034
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| Research Category |
Grant-in-Aid for Co-operative Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
SUZUKI Koichi Tokyo Metropolitan Institute of Medical, 遺伝子情報部, 部長 (80011948)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Kenji Univ. Tokyo, Dept. SCience, Prof., 理学部・生物雑学科, 教授 (70011533)
ICHIHARA Akira Univ. Tokushima, Enzyme Inst. Prof., 酵素科学センター, 教授 (20035405)
SUGITA Hideo Natl. Inst. Neurology, President, 所長 (80009951)
KATO Keitaro Univ. Kyushu, Dept. Pharmacol., Prof., 薬学部, 教授 (70037571)
KATUNUMA Nobuhiko Univ. Tokushima, Enzyme Inst., Prof., 酵素科学センター, 教授 (50035375)
村地 孝 京都大学, 医学部, 教授 (10089104)
佐々木 實 名古屋市立大学, 医学部, 教授 (10080003)
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥21,100,000 (Direct Cost: ¥21,100,000)
Fiscal Year 1990: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1989: ¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1988: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Keywords | Protease / calpain / cathepsin / proteasome / gene expression / アテプシン / 病態 / プロテアーゼ / プロテアーゼインヒビター / カルシウムプロテアーゼ / ATPプロテアーゼ / プロセシング |
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| Research Abstract |
1. Calcium-dependent protease
Functional analysis of the 5'-upstream region of the human calpain large subunit gene revealed that the presence of a functional TRE sequence. The results of the analyses of expression of the calpain gene indicated that the level of m-calpain is changed by various stimuli whereas that of mu-calpain stays constant. mu-calpain presumably plays house-keeping functions while mcalpain functions in signal response.
2. Lysosomal proteases
The gene structures of cathepsins H and L were determined and their gene expression was examined. The expression of these proteases was induced by both cAMP and TPA. significant amount of cathepsin L is secreted from cancer cells into medium, suggesting its functional importance in metastasis.
3. Multicatalytic proteinase (Proteasome)
cDNA cloning of subunits of proteasome from human, rat and yeast has been performed. Although more than 10 subunits have been cloned, none of them shows sequence similarity to other known proteases. Among 3 yeast subunits thus far cloned, one is not essential for growth, although the other two are indispensable. Gene disruption experiments are now in progress to clarify the function of the non-essential subunit in the proteasome function.
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