Proteasome condensate formation is driven by multivalent interactions with shuttle factors and ubiquitin chains

• 成果类型: Article
• 署名作者: Waite, Kenrick A.; Vontz, Gabrielle; Lee, Stella Y.; Roelofs, Jeroen
• 署名单位: Louisiana State University System; Louisiana State University Health Sciences Center New Orleans; University of Kansas; University of Kansas Medical Center
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12840
• DOI: 10.1073/pnas.2310756121
• 发表日期: 2024-03-01
• 关键词: storage granules; proteins; yeast; rad23; autophagy; domains; degradation; inhibition; receptor; localization

摘要

Stress conditions can cause the relocalization of proteasomes to condensates in yeast and mammalian cells. The interactions that facilitate the formation of proteasome condensates, however, are unclear. Here, we show that the formation of proteasome condensates in yeast depends on ubiquitin chains together with the proteasome shuttle factors Rad23 and Dsk2. These shuttle factors colocalize to these condensates. Strains deleted for the third shuttle factor gene, DDI1, show proteasome condensates in the absence of cellular stress, consistent with the accumulation of substrates with long K48- linked ubiquitin chains that accumulate in this mutant. We propose a model where the long K48-linked ubiquitin chains function as a scaffold for the ubiquitin- binding domains of the shuttle factors and the proteasome, allowing for the multivalent interactions that further drive condensate formation. Indeed, we determined different intrinsic ubiquitin receptors of the proteasome-Rpn1, Rpn10, and Rpn13-and the Ubl domains of Rad23 and Dsk2 are critical under different condensate- inducing conditions. In all, our data support a model where the cellular accumulation of substrates with long ubiquitin chains, potentially due to reduced cellular energy, allows for proteasome condensate formation. This suggests that proteasome condensates are not simply for proteasome storage, but function to sequester soluble ubiquitinated substrates together with inactive proteasomes.