Protein synthesis quality control system (PSQC)

The protein synthesis quality control (PSQC) system is a multi-layered network of cellular pathways responsible for maintaining the integrity of the proteome by monitoring protein production, folding, and degradation (Balch et al., 2008, Science). It includes ribosome-associated quality control (RQC), which detects stalled translation and targets nascent chains for degradation, and the unfolded protein response (UPR), which manages protein folding stress in the endoplasmic reticulum (Brandman & Hegde, 2016, Nat Rev Mol Cell Biol; Walter & Ron, 2011, Science). These pathways utilize molecular chaperones to facilitate folding and the ubiquitin-proteasome system (UPS) or autophagy to eliminate defective proteins. Failure of the PSQC leads to the accumulation of misfolded proteins and aggregates, a primary driver of neurodegenerative diseases such as Alzheimer's and Parkinson's (Hipp et al., 2019, Nat Rev Mol Cell Biol). Conversely, cancer cells often upregulate PSQC components to survive high levels of protein synthesis and mutation-induced stress, making these pathways attractive targets for chemotherapy. Drugs like bortezomib target the proteasome, while others target chaperones like Hsp90 or UPR sensors like PERK to disrupt proteostasis in diseased cells (Deshaies, 2014, Nature).

Other names

Proteostasis networkProtein quality controlPQCRibosome-associated quality controlRQCmRNA surveillanceEndoplasmic reticulum-associated degradationERADUnfolded protein responseUPR

Modulation of protein folding, degradation, and translation fidelity through inhibition or activation of specific nodes such as the proteasome, molecular chaperones, or the unfolded protein response (UPR) sensors.