Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Department of Chemical and Biomolecular Engineering, Tulane University, New Orleans, LA 70118, United States.
Curr Opin Biotechnol. 2014 Dec;30:168-77. doi: 10.1016/j.copbio.2014.06.018. Epub 2014 Jul 15.
The emergence of genomic approaches coupled to recombinant DNA technologies have identified the quality control systems that regulate proteostasis - biological pathways that modulate protein biogenesis, maturation, trafficking, and degradation. The elucidation of these pathways has become of growing importance in therapeutics as loss of proteostasis has been suggested to lead to a number of human diseases including Alzheimer's, Parkinson's Disease and Type II Diabetes. We anticipate that the most successful strategies for protein expression and therapeutics development may involve integration of protein engineering strategies with host manipulation, to exploit the cell's native stress response pathways and trafficking mechanisms. This review will highlight recent findings and mechanistic detail correlated to quality control in the early secretory pathway of Saccharomyces cerevisiae.
基因组方法的出现加上重组 DNA 技术,已经确定了调节蛋白质稳定性的质量控制系统——这些生物途径调节着蛋白质的生物发生、成熟、运输和降解。这些途径的阐明在治疗学中变得越来越重要,因为蛋白质稳定性的丧失被认为会导致许多人类疾病,包括阿尔茨海默病、帕金森病和 2 型糖尿病。我们预计,蛋白质表达和治疗开发最成功的策略可能涉及将蛋白质工程策略与宿主操作相结合,以利用细胞的天然应激反应途径和运输机制。这篇综述将重点介绍与酿酒酵母早期分泌途径中的质量控制相关的最新发现和机制细节。