The Role of Molecular Chaperones in Foreign Protein Secretion in Yeast

9500238 Wise主要研究者（PI）建议研究蛋白质折叠伴侣在酵母分泌外源蛋白中的作用。 文献中有证据表明，内质网内腔中的蛋白质折叠可能是整个分泌过程中的限速步骤，并且分子伴侣如蛋白质二硫键异构酶（PDI）和KAR 2（哺乳动物重链结合蛋白的酵母同系物）在细胞内蛋白质折叠中起关键作用。 PI计划通过使用受调节的启动子来改变PDI和KAR 2的细胞内水平，并确定对外源蛋白分泌的影响。 PI还计划通过筛选重组DNA文库中的基因来分离新型分子伴侣，这些基因的过表达增强了外源蛋白分泌或补充了蛋白易位进入分泌途径中的遗传诱导缺陷。 ***

9500238 Wise The Principal Investigators (PIs) propose to study the role of protein folding chaperones in the secretion of foreign proteins from yeast. There is evidence in the literature that protein folding in the lumen of the endoplasmic reticulum may be the rate-limiting step in the overall process of secretion, and that chaperones such as protein disulfide isomerase (PDI) and KAR2 (the yeast homolog of mammalian heavy chain binding protein) play a key role in intracellular protein folding. The PIs plan to vary intracellular levels of PDI and KAR2 by use of regulated promoters, and to determine the resulting effects on foreign protein secretion. The PIs also plan to isolate novel chaperones by screening recombinant DNA libraries for genes whose overexpression enhances foreign protein secretion or complements a genetically induced defect in protein translocation into the secretory pathway. ***