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  Stress- and ubiquitylation-dependent phase separation of the proteasome

Yasuda, S., Tsuchiya, H., Kaiho, A., Guo, Q., Ikeuchi, K., Endo, A., et al. (2020). Stress- and ubiquitylation-dependent phase separation of the proteasome. NATURE, 578, 296-300. doi:10.1038/s41586-020-1982-9.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-C689-1 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-C68A-0
Genre: Journal Article

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 Creators:
Yasuda, Sayaka1, Author
Tsuchiya, Hikaru1, Author
Kaiho, Ai1, Author
Guo, Qiang2, Author              
Ikeuchi, Ken1, Author
Endo, Akinori1, Author
Arai, Naoko1, Author
Ohtake, Fumiaki1, Author
Murata, Shigeo1, Author
Inada, Toshifumi1, Author
Baumeister, Wolfgang1, Author
Fernandez-Busnadiego, Ruben2, Author              
Tanaka, Keiji1, Author
Saeki, Yasushi1, Author
Affiliations:
1external, ou_persistent22              
2Baumeister, Wolfgang / Molecular Structural Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565142              

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Free keywords: 26S PROTEASOME; REVEALS; TOOLBOX; LOCALIZATION; DEGRADATION; SPECIFICITY; SOFTWARE; DYNAMICS
 Abstract: The proteasome is a major proteolytic machine that regulates cellular proteostasis through selective degradation of ubiquitylated proteins(1,2). A number of ubiquitin-related molecules have recently been found to be involved in the regulation of biomolecular condensates or membraneless organelles, which arise by liquid-liquid phase separation of specific biomolecules, including stress granules, nuclear speckles and autophagosomes(3-8), but it remains unclear whether the proteasome also participates in such regulation. Here we reveal that proteasome-containing nuclear foci form under acute hyperosmotic stress. These foci are transient structures that contain ubiquitylated proteins, p97 (also known as valosin-containing protein (VCP)) and multiple proteasome-interacting proteins, which collectively constitute a proteolytic centre. The major substrates for degradation by these foci were ribosomal proteins that failed to properly assemble. Notably, the proteasome foci exhibited properties of liquid droplets. RAD23B, a substrate-shuttling factor for the proteasome, and ubiquitylated proteins were necessary for formation of proteasome foci. In mechanistic terms, a liquid-liquid phase separation was triggered by multivalent interactions of two ubiquitin-associated domains of RAD23B and ubiquitin chains consisting of four or more ubiquitin molecules. Collectively, our results suggest that ubiquitin-chain-dependent phase separation induces the formation of a nuclear proteolytic compartment that promotes proteasomal degradation. Hyperosmotic stress leads to a phase separation of the proteasome, triggered by interactions between RAD23B and ubiquitylated proteins, which bring together p97 and proteasome-associated proteins into nuclear proteolytic foci.

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Language(s): eng - English
 Dates: 2020-02
 Publication Status: Published online
 Pages: 5
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000511285700001
DOI: 10.1038/s41586-020-1982-9
 Degree: -

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Title: NATURE
Source Genre: Journal
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Publ. Info: MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND : NATURE PUBLISHING GROUP
Pages: - Volume / Issue: 578 Sequence Number: - Start / End Page: 296 - 300 Identifier: ISSN: 0028-0836