Degradation of dysfunctional, damaged, or misfolded proteins is a crucial component of the protein quality control network to maintain cellular proteostasis. Dysfunction in proteostasis regulation due to imbalances in protein synthesis, folding, and degradation challenges the integrity of the cellular proteome and favors the accumulation of aggregated proteins that can damage cells by a loss of their functions and/or a gain of adverse functions. Ubiquitination is an essential player in proteostasis regulation but also in orchestrating signaling pathways in response to various stress conditions. Both cellular degradation systems, the proteasome and autophagy, employ ubiquitin for selection and targeting of substrates to the degradative machineries. Here we summarize the manifold functions of ubiquitin in protein degradation and discuss its emerging role in the formation of biomolecular condensates through liquid-liquid phase separation, which allows spatiotemporal regulation of protein quality control.

功能失调、受损或错误折叠的蛋白质的降解是蛋白质质量控​​制网络中维持细胞蛋白质稳态的关键组成部分。由于蛋白质合成、折叠和降解的不平衡导致的蛋白质稳态调节功能障碍挑战了细胞蛋白质组的完整性，并有利于聚集蛋白质的积累，这些蛋白质可能通过丧失功能和/或获得不利功能来损害细胞。泛素化是蛋白质稳态调节的重要参与者，也是协调信号通路以应对各种压力条件的重要参与者。蛋白酶体和自噬这两种细胞降解系统都使用泛素来选择和靶向降解机制的底物。