{"title":"Protein quality control machinery: regulators of condensate architecture and functionality.","authors":"Anitha Rajendran, Carlos A Castañeda","doi":"10.1016/j.tibs.2024.12.003","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":" ","pages":""},"PeriodicalIF":11.6000,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in Biochemical Sciences","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.tibs.2024.12.003","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
For over 40 years, Trends in Biochemical Sciences (TIBS) has been a leading publication keeping readers informed about recent advances in all areas of biochemistry and molecular biology. Through monthly, peer-reviewed issues, TIBS covers a wide range of topics, from traditional subjects like protein structure and function to emerging areas in signaling and metabolism. Articles are curated by the Editor and authored by top researchers in their fields, with a focus on moving beyond simple literature summaries to providing novel insights and perspectives. Each issue primarily features concise and timely Reviews and Opinions, supplemented by shorter articles including Spotlights, Forums, and Technology of the Month, as well as impactful pieces like Science & Society and Scientific Life articles.