Chaperones and multitasking proteins in the nucleolus: networking together for survival?

The nucleolus has emerged as a key player that regulates cell growth, survival and the recovery from stress. Progress in proteomics made it possible to sequence the nucleolar proteome under different physiological conditions. Together with other research, this work revealed the presence of multiple chaperones and co-chaperones in the nucleolus. Molecular chaperones are components of a larger network that promotes protein homeostasis, thereby providing continuous adaptation to a changing environment. Recent studies suggest that the cellular chaperone network is divided into individual branches which orchestrate specific functions. Input from separate branches is then combined to 'fine-tune' the cellular proteostasis network. Based on the latest developments in nucleolar and chaperone biology, we speculate that a unique network comprising chaperones, co-chaperones and multitasking proteins is located in nucleoli. This network supports and regulates fundamental biological processes, including ribosome biogenesis, cell signaling, and the stress response.