J proteins direct the processing of misfolded proteins within cellular protein quality control

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**All proteins need to*acquire their defined three-dimensional conformation in order to function*properly, a process termed protein folding. Protein folding can be challenged*by numerous environmental and genetic assaults resulting in misfolded proteins*that are usually dysfunctional and often toxic to the cell. Cellular protein*quality control, i.e. all mechanisms involved in protein synthesis,*maintenance, and degradation, has thus evolved in all living cells to protect*cells from the detrimental consequences of protein misfolding. Molecular*chaperones of the J protein class are key players in cellular protein quality*control as they facilitate proper protein synthesis, maintenance, and*degradation. J proteins constitute the most diverse class of molecular chaperones as the*number of different J proteins in all organism that have been analyzed so far*exceeds the number of all other molecular chaperone. This perplexing diversity*implies that J proteins evolved to selectively target client proteins and*execute specialized functions within the cellular protein quality control*network. Yet the molecular and cellular mechanisms underpinning this target specificity*and the distinct cellular functions of individual J proteins remain unclear. Our*research program proposed here aims to determine the target specificity and*distinct cellular roles of J proteins by applying a combination of genetic,*systems biology, cell biological and computational approaches using yeast (Saccharomyces*cerevisiae) as a genetically tractable model organism. Our research will*determine general biological principles by which J proteins specify the*activity of cellular protein quality control and thus execute functionally*distinct roles in living cells.****