Rajendran Anitha, Castañeda Carlos A
Department of Chemistry, Syracuse University, Syracuse, NY 13244, USA.
Department of Chemistry, Syracuse University, Syracuse, NY 13244, USA; Department of Biology, Syracuse University, Syracuse, NY 13244, USA; Bioinspired Institute, Syracuse University, Syracuse, NY 13244, USA; Interdisciplinary Neuroscience Program, Syracuse University, Syracuse, NY 13244, USA.
Trends Biochem Sci. 2025 Feb;50(2):106-120. doi: 10.1016/j.tibs.2024.12.003. Epub 2025 Jan 3.
Protein quality control (PQC) mechanisms including the ubiquitin (Ub)-proteasome system (UPS), autophagy, and chaperone-mediated refolding are essential to maintain protein homeostasis in cells. Recent studies show that these PQC mechanisms are further modulated by biomolecular condensates that sequester PQC components and compartmentalize reactions. Accumulating evidence points towards the PQC machinery playing a pivotal role in regulating the assembly, disassembly, and viscoelastic properties of several condensates. Here, we discuss how the PQC machinery can form their own condensates and also be recruited to known condensates under physiological or stress-induced conditions. We present molecular insights into how the multivalent architecture of polyUb chains, Ub-binding adaptor proteins, and other PQC machinery contribute to condensate assembly, leading to the regulation of downstream PQC outcomes and therapeutic potential.
蛋白质质量控制（PQC）机制，包括泛素（Ub）-蛋白酶体系统（UPS）、自噬和伴侣介导的重折叠，对于维持细胞内蛋白质稳态至关重要。最近的研究表明，这些PQC机制会受到生物分子凝聚物的进一步调控，这些凝聚物会隔离PQC组分并使反应分区化。越来越多的证据表明，PQC机制在调节几种凝聚物的组装、拆卸和粘弹性特性方面起着关键作用。在这里，我们讨论了PQC机制如何形成它们自己的凝聚物，以及在生理或应激诱导条件下如何被招募到已知的凝聚物中。我们提供了分子层面的见解，说明多聚泛素链、Ub结合衔接蛋白和其他PQC机制的多价结构如何促成凝聚物组装，从而导致对下游PQC结果的调控以及治疗潜力。
