The unfolded protein response regulates multiple aspects of secretory and membrane protein biogenesis and endoplasmic reticulum quality control

被引:267
作者
Ng, DTW [1 ]
Spear, ED
Walter, P
机构
[1] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA USA
[2] Univ Calif San Francisco, Dept Biochem & Biophys, Sch Med, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Howard Hughes Med Inst, Sch Med, San Francisco, CA 94143 USA
关键词
protein translocation; protein maturation; gene regulation; glycosylation; protein degradation;
D O I
10.1083/jcb.150.1.77
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The unfolded protein response (UPR) is an intracellular signaling pathway that relays signals from the lumen of the ER to activate target genes in the nucleus. We devised a genetic screen in the yeast Saccharomyces cerevisiae to isolate mutants that are dependent on activation of the pathway for viability. Using this strategy, we isolated mutants affecting various aspects of ER function, including protein translocation, folding, glycosylation, glycosylphosphatidylinositol modification, and ER-associated protein degradation (ERAD). Extending results gleaned from the genetic studies, we demonstrate that the UPR regulates trafficking of proteins at the translocon to balance the needs of biosynthesis and ERAD. The approach also revealed connections of the UPR to other regulatory pathways. In particular, we identified SON1/RPN4, a recently described transcriptional regulator for genes encoding subunits of the proteasome. Our genetic strategy, therefore, offers a powerful means to provide insight into the physiology of the UPR and to identify novel genes with roles in many aspects of secretory and membrane protein biogenesis.
引用
收藏
页码:77 / 88
页数:12
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