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 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.