Lactacystin, a Proteasome Inhibitor : Discovery and its Application in Cell Biology
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概要
- 論文の詳細を見る
Lactacystin was isolated from the culture broth of Streptomyces lactacystinaeus as an inducer of neurite outgrowth in Neuro 2a cells (a mouse neuroblastoma cell line). The structure of lactacystin, elucidated by spectroscopic analyses including NMR and X-ray crystallography, possesses a non-peptide skeleton consisting of two α-amino acids, N-acetylcysteine and a novel pyroglutamic acid derivative. Extensive studies on its mode of action revealed that lactacystin inhibits proteasome, a high molecular weight, multicatalytic protease complex responsible for most non-lysosomal intracellular protein degradation, by binding covalently to the active site N-terminal threonine residue in certain β-subunits of proteasome. Lactacystin and its cell-permeable β-lactone form, later designated omuralide by Prof. E. J. Corey, which are structurally different from the synthetic peptide aldehydes, are much more specific proteasome inhibitors. The demonstration of this lactacystin action gave decisive understanding of proteasome as a novel threonine protease. Since then, specific inhibitors have allowed researchers to simplify studies of proteasome functions, leading to many unexpected findings about the importance of the ubiquitin-proteasome pathway in various cellular processes, such as cell cycle, apoptosis, antigen presentation and the degradation of regulatory or membrane proteins. In this review, potential biomedical applications are also described.
- 公益社団法人日本薬学会の論文
- 2000-10-01
著者
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Omura Satoshi
Research Center For Biological Function The Kitasato Institute And School Of Pharmaceutical Sciences
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Tomoda Hiroshi
Research Center For Biological Function The Kitasato Institute And Graduate School Of Pharmaceutical
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Tomoda Hiroshi
Research Center For Biological Function The Kitasatc Institute
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Omura Satoshi
Research Center For Biological Function The Kitasato Institute And Graduate School Of Pharmaceutical
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Omura Satoshi
Research Center For Biological Function The Kitasato Institute
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