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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

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Volume 393, Issue 4


The proteasome: molecular machinery and pathophysiological roles

Keiji Tanaka
  • Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Kamikitazawa 2-1-6, Setagaya-ku, Tokyo 156-8506, Japan
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/ Tsunehiro Mizushima
  • Picobiology Institute, Department of Life Science, Graduate School of Life Science, University of Hyogo, 3-2-1, Kouto, Kamigori-cho, Ako-gun, Hyogo 678-1297, Japan
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/ Yasushi Saeki
  • Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Kamikitazawa 2-1-6, Setagaya-ku, Tokyo 156-8506, Japan
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The 26S proteasome, in collaboration with ubiquitin, operates the energy-dependent regulated proteolysis process in eukaryotic cells. Over the past 30 years, several studies have comprehensively characterized the structure and molecular/physiological functions of the 26S proteasome. It is a sophisticated 2.5-MDa protein degradation machine comprising a proteolytic core particle (CP) and one or two terminal regulatory particle(s) (RP). The CP consists of two outer α rings and two inner β rings, which are made up of seven structurally similar α and β subunits, respectively. The CP contains catalytic threonine residues (β1, β2, and β5; caspase-like, trypsin-like, and chymotrypsin-like activities, respectively) on the inner surface of the chamber formed by two abutting β rings. Intriguingly, the immunotype proteasomes, named ‘immunoproteasome’ and ‘thymoproteasome’, whose catalytic subunits are replaced by the related counterparts, were discovered lately. Both unique isoenzymes essentially contribute to the acquisition of adaptive immunity in vertebrates. The RP, which serves to recognize polyubiquitylated substrate proteins and plays a role in their deubiquitylating, unfolding, and translocation into the interior of the CP for destruction, forms two subcomplexes: the base and the lid. On another front, the PA28 and PA200, alternative CP activator proteins discovered biochemically, both play independent roles in proteolysis of the 26S proteasome. Several studies have highlighted the importance of the proteasome in various intractable diseases that have been increasing in the aged society of the 21st century.

Keywords: 20S and 26S proteasomes; immunoproteasome; RP; thymoproteasome; ubiquitin

About the article

Corresponding author

Received: 2011-12-12

Accepted: 2012-02-08

Published in Print: 2012-04-01

Citation Information: Biological Chemistry, Volume 393, Issue 4, Pages 217–234, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2011-0285.

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©2012 by Walter de Gruyter Berlin Boston. Copyright Clearance Center

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