Interactions of the proteasomal system with chaperones: protein triage and protein quality control

Unfolded, misfolded, or modified proteins are able to induce proteotoxic cell stress. To prevent proteotoxic stress, it is crucial to have a functional protein quality control system, especially in the cytosol and in the endoplasmic reticulum where proteins are newly synthesized. The leading actors in this protein quality control system are the ubiquitin-proteasomal system and the huge family of heat shock proteins and chaperones. Both systems interact with each other, influencing the decision of whether a protein becomes (re)folded or degraded. Especially upon cellular stress, such as heat shock or oxidative stress, heat shock proteins are drastically upregulated, supporting, and regulating proteasomal degradation of defect proteins. Failure of one of the systems can be compensated partially by the upregulation of the other. Nevertheless, prolonged failure of the proteasome or chaperones results in protein aggregation and cellular dysfunction.