| Co-Investigator(Kenkyū-buntansha) |
YASHIRODA Hideki The Tokyo Metropolitan, Institute of Medical Science, Researcher, 東京都臨床医学綜合研究所, 研究員 (20311425)
YOSHIDA Yukiko The Tokyo Metropolitan, Institute of Medical Science, Researcher, 東京都臨床医学綜合研究所, 研究員 (90271543)
MURATA Shigeo The Tokyo Metropolitan, Institute of Medical Science, Researcher, 東京都臨床医学綜合研究所, 研究員 (20344070)
KOMATSU Masaaki The Tokyo Metropolitan, Institute of Medical Science, Researcher, 東京都臨床医学綜合研究所, 研究員 (90356254)
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| Research Abstract |
The proteasome (a eukaryotic ATP-dependent protease complex) is a sophisticated cellular apparatus capable of shredding unnecessary proteins modified by ubiquitin (a posttranslational modifier serving a destination signal for proteolysis) selectively. It plays a central role in the control of a diverse array of cellular activities by catalyzing biological reactions rapidly, orderly, exhaustively, and uni-directionally. Over the past 25 years, we have been aiming to elucidate comprehensively the divergent roles of the ubiquitin-proteasome system (UPS) in the life science field. In the present project named "Studies on proteolysis mediated by the proteasomes and ubiquitin", our research projects on the proteasomes were (1) the analysis of the tertiary structure of the mammalian proteasome as a unusually large multi-protein complex, (2) the clarification of assembling mechanisms, focusing on the newly-discovered PAC (proteasome assembling chaperone) 1/2 heterodimeric complex and Hsp90, and (3) immunogenetic analysis of the new proteasome activator family proteins of PA28α, PA28β and PA28γ. In the ubiquitin project, we were interested in analyzing the quality-control ubiquitin-protein ligases (E3s) in cells: CHIP is a molecular chaperone-dependent E3, Parkin is encoded by the causative gene of eating of oneself") and two novel ubiquitin-like (UBL) modifying systems, such as NEDD8 and Ufml pathways, by generation of model mice with impairment of various related genes. Recently, various diseases, such as cancers, infectious diseases, and neurodegenerative diseases, have been increasing in the aged society of the 21st century. Considering such circumstances, it has been clarified, as a central scenario, that dysfunctioning of UPS causes these intractable diseases. Thus, our studies may contribute to the development of new bio-science field as well as to that of therapies for intractable diseases.
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