TY - JOUR
T1 - Protein quality control machinery
T2 - regulators of condensate architecture and functionality
AU - Rajendran, Anitha
AU - Castañeda, Carlos A.
N1 - Publisher Copyright:
© 2024 Elsevier Ltd
PY - 2025/2
Y1 - 2025/2
N2 - 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.
AB - 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.
KW - chaperones
KW - condensates
KW - phase separation
KW - polyphasic linkage
KW - protein quality control
KW - ubiquitination
UR - http://www.scopus.com/inward/record.url?scp=85214028504&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85214028504&partnerID=8YFLogxK
U2 - 10.1016/j.tibs.2024.12.003
DO - 10.1016/j.tibs.2024.12.003
M3 - Review article
AN - SCOPUS:85214028504
SN - 0968-0004
VL - 50
SP - 106
EP - 120
JO - Trends in Biochemical Sciences
JF - Trends in Biochemical Sciences
IS - 2
ER -