Quality control of protein complex assembly by the ubiquitin–proteasome system

The majority of human proteins operate as multimeric complexes with defined compositions and distinct architectures. How the assembly of these complexes is surveyed and how defective complexes are recognized is just beginning to emerge. In eukaryotes, over 600 E3 ubiquitin ligases form part of the u...

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Bibliographic Details
Published in:Trends in cell biology 2022-08, Vol.32 (8), p.696-706
Main Authors: Pla-Prats, Carlos, Thomä, Nicolas H.
Format: Article
Language:English
Subjects:
AQC
assembly
protein complex
quality control
ubiquitin
UPS
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Summary:The majority of human proteins operate as multimeric complexes with defined compositions and distinct architectures. How the assembly of these complexes is surveyed and how defective complexes are recognized is just beginning to emerge. In eukaryotes, over 600 E3 ubiquitin ligases form part of the ubiquitin–proteasome system (UPS) which detects structural characteristics in its target proteins and selectively induces their degradation. The UPS has recently been shown to oversee key quality control steps during the assembly of protein complexes. We review recent findings on how E3 ubiquitin ligases regulate protein complex assembly and highlight unanswered questions relating to their mechanism of action. The majority of human proteins function as part of multimeric protein complexes.Subunit stoichiometry in vivo is highly variable, and a significant fraction of the proteome arises from non-stoichiometric synthesis.The ubiquitin–proteasome system (UPS) can detect failures in complex assembly and target unassembled or incorrectly assembled complexes for degradation.Key cellular complexes such as hemoglobin, BTB (broad complex, Tramtrack, and Bric-à-brac) dimers, the proteasome, and the ribosome have recently been shown to undergo assembly quality control (AQC).AQC safeguards cellular function and health.
ISSN:0962-8924
1879-3088
DOI:10.1016/j.tcb.2022.02.005