Abstract

The continuous refreshment of the proteome is critical to maintain protein homeostasis and to adapt cells to changing conditions. Thus, de novo protein biogenesis by ribosomes is vitally important to every cellular system. This process is delicate and error-prone and requires, besides cytosolic chaperones, the guidance by a specialized set of molecular chaperones including the bacterial trigger factor (TF), the archaeal and eukaryotic nascent polypeptide-associated complex (NAC), and the eukaryotic ribosome-associated complex (RAC). These chaperones bind transiently to the translation machinery and the nascent protein to support early folding events and to regulate cotranslational protein transport. Moreover, recent findings indicate that NAC is also a very potent suppressor of aggregation and proteotoxicity in vivo and in vitro of mutant PolyQ-expanded proteins associated with human diseases like Huntington’s disease and spinocerebellar ataxias. In my talk I will focus on the most recent findings about NAC and its potential mechanisms of action in health and disease.