Phase separation of polyubiquitinated proteins in UBQLN2 condensates controls substrate fate

• 成果类型: Article
• 署名作者: Valentino, Isabella M.; Llivicota-Guaman, Jeniffer G.; Dao, Thuy P.; Mulvey, Erin O.; Lehman, Andrew M.; Galagedera, Sarasi K. K.; Mallon, Erica L.; Castaneda, Carlos A.; Kraut, Daniel A.
• 署名单位: Villanova University; Syracuse University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9518
• DOI: 10.1073/pnas.2405964121
• 发表日期: 2024-08-13
• 关键词: 26s proteasome; chain; SYSTEM

摘要

Ubiquitination is one of the most common posttranslational modifications in eukaryotic cells. Depending on the architecture of polyubiquitin chains, substrate proteins can meet different cellular fates, but our understanding of how chain linkage controls protein fate proteins and to the proteasome or other protein quality control machinery elements and play a role in substrate fate determination. Under physiological conditions, UBQLN2 forms biomolecular condensates through phase separation, a physicochemical phenomenon in which multivalent interactions drive the formation of a macromolecule- rich dense phase. Ubiquitin and polyubiquitin chains modulate UBQLN2's phase separation in a linkage- dependent manner, suggesting a possible link to substrate fate determination, but polyubiquitinated substrates have not been examined directly. Using sedimentation assays and microscopy we show that polyubiquitinated substrates induce UBQLN2 phase separation and incorporate into the resulting condensates. This substrate effect is preter of the ubiquitin code.