2000 Fiscal Year Final Research Report Summary
BIOMODULATOR FUNCTIONS OF PROTEOLYSIS
| Project/Area Number |
08278103
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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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| Research Institution | JUNTENDO UNIVERITY |
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Principal Investigator |
KOMINAMI Eiki JUNTENDO UNIVERSITY SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (10035496)
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| Co-Investigator(Kenkyū-buntansha) |
WASHIMA Seiichika TOKYO METROPOLITAN INSTITUTE FOR MEDICAL SCIENCE, HEAD, 部長 (60008571)
NATORI Shunji NATORI SPECIAL LABORATORY, INSTITUTE OF PHYSICAL AND CHEMICAL RESEARCH (RIKEN), CHIEF SCIENTIST, 名取特別研究室, 特別招聘研究員 (50012662)
YOKOSAWA Yoshihide GRADUATE SCHOOL OF PHARMACEUTICAL SCIENCES, HOKKAIDO UNIVERSITY, PROFESSOR, 大学院・薬学研究科, 教授 (90012765)
UCHIYAMA Yasuo OSAKA UNIVERSITY GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学研究科, 教授 (10049091)
OHSUMI Yoshinori NATIONAL INSTITUTE FOR BASIC BIOLOGY, PROFESSOR, 教授 (30114416)
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| Project Period (FY) |
1996 – 1999
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| Keywords | BIOMODULATOR / PROTEOLYSIS / LYSOSOME / AUTOPHAGY / CONJUGATION SYSTEM / CATHEPSIN / APOPTOSIS / CASPASE |
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| Research Abstract |
Biomodulator functions of intracellular proteolytic systems have been studied and following results were obtained. 1.lysosomal/vacuolar system : Macroautophagy mediates the bulk turnover of cytoplasmic material during starvation conditions. Ohsumi isolated 16 genes required for autophagy in yeast and has shown some of the molecular hallmarks of the autophagic pathway, including the role of two novel conjugation systems. The systems essential for the completion of autophagosomes include Apg12p and Apg8p as modifiers and Apg7p, Apg10p and Apg3p for conjugation enzymes. The mechanistic features of these conjugation systems are reminiscent of the proteasome-mediated degradation of substrates covalently tagged by ubiquitin. Kominami has been recently characterized mammalian homologs of some of the yeast autophagy proteins. These studies may provide further insight into the mechanism of mammalian macroautophagy. Kominami and Uchiyama showed that deficiency of a lysosomal proteinase, TPP-I or cathepsin D causes lysosomal storage of a hydrophobic protein, finally leading to late infantile form of neuronal ceroid lipofuscinosis, or a new type of this disease, respectively. Natori has shown importance of proteolysis by cathepsins B and L during metamorphosis of Sarcophagia. 2.Knockout mice of caspase-11 and caspases-1, 3, 7 and 9 were produced by Miura and Kuida, respectively and their biological functions and activation cascades were analysed. Involvement of calpain and proteasome systems in caspase-dependent apoptosis and caspase-independent apoptosis were also analysed.
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