Engineering of chaperone systems and of the unfolded protein response

被引:37
作者
Khan, Saeed U. [1 ]
Schroeder, Martin [1 ]
机构
[1] Univ Durham, Sch Biol & Biomed Sci, Durham DH1 3LE, England
基金
英国生物技术与生命科学研究理事会; 英国惠康基金;
关键词
Endoplasmic reticulum associated protein degradation; Heterologous protein production; Molecular chaperone; Protein folding; Unfolded protein response;
D O I
10.1007/s10616-008-9157-9
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Production of recombinant proteins in mammalian cells is a successful technology that delivers protein pharmaceuticals for therapies and for diagnosis of human disorders. Cost effective production of protein biopharmaceuticals requires extensive optimization through cell and fermentation process engineering at the upstream and chemical engineering of purification processes at the downstream side of the production process. The majority of protein pharmaceuticals are secreted proteins. Accumulating evidence suggests that the folding and processing of these proteins in the endoplasmic reticulum (ER) is a general rate- and yield limiting step for their production. We will summarize our knowledge of protein folding in the ER and of signal transduction pathways activated by accumulation of unfolded proteins in the ER, collectively called the unfolded protein response (UPR). On the basis of this knowledge we will evaluate engineering approaches to increase cell specific productivities through engineering of the ER-resident protein folding machinery and of the UPR.
引用
收藏
页码:207 / 231
页数:25
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