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

** 所有蛋白质都需要 * 获得它们定义的三维构象，以便正常发挥功能，这一过程称为蛋白质折叠。蛋白质折叠可以受到许多环境和遗传攻击的挑战，导致错误折叠的蛋白质，这些蛋白质通常是功能失调的，并且通常对细胞有毒。细胞蛋白质质量控制，即蛋白质合成、维持和降解的所有机制，因此在所有活细胞中进化，以保护细胞免受蛋白质错误折叠的有害后果。J蛋白类分子伴侣在细胞蛋白质质量控制中起关键作用，因为它们促进蛋白质的适当合成、维持和降解。J蛋白构成了最多样化的一类分子伴侣，因为迄今为止已分析的所有生物体中不同J蛋白的数量超过了所有其他分子伴侣的数量。这种令人困惑的多样性 * 意味着J蛋白进化为选择性地靶向客户蛋白，并 * 在细胞蛋白质质量控制 * 网络中执行专门的功能。然而，支持这种靶特异性的分子和细胞机制 * 以及单个J蛋白的独特细胞功能仍不清楚。我们的研究计划在这里提出的目的是确定目标的特异性和不同的细胞作用的J蛋白通过应用遗传学，系统生物学，细胞生物学和计算方法的组合使用酵母（酿酒酵母）作为一个遗传上易处理的模式生物。我们的研究将确定J蛋白指定细胞蛋白质质量控制活性的一般生物学原理，从而在活细胞中执行功能上不同的角色。

**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.****