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| Title | Stress- and ubiquitylation-dependent phase separation of the proteasome. |
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| Journal, issue, pages | Nature, Vol. 578, Issue 7794, Page 296-300, Year 2020 |
| Publish date | Feb 5, 2020 |
 Authors | Sayaka Yasuda / Hikaru Tsuchiya / Ai Kaiho / Qiang Guo / Ken Ikeuchi / Akinori Endo / Naoko Arai / Fumiaki Ohtake / Shigeo Murata / Toshifumi Inada / Wolfgang Baumeister / Rubén Fernández-Busnadiego / Keiji Tanaka / Yasushi Saeki /   |
| PubMed Abstract | The proteasome is a major proteolytic machine that regulates cellular proteostasis through selective degradation of ubiquitylated proteins. A number of ubiquitin-related molecules have recently been ...The proteasome is a major proteolytic machine that regulates cellular proteostasis through selective degradation of ubiquitylated proteins. 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, 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. |
 External links | Nature / PubMed:32025036 |
| Methods | EM (tomography) |
| Structure data |  EMDB-10494: |
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Homo sapiens (human)