Endoplasmic reticulum-associated degradation

被引:262
作者
Römisch, K [1 ]
机构
[1] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 2XY, England
基金
英国惠康基金;
关键词
protein secretion; protein misfolding; Sec61; channel; retrotranslocation; proteasome;
D O I
10.1146/annurev.cellbio.21.012704.133250
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Secretory and transmembrane proteins enter the secretory pathway through the protein-conductin Sec61 channel in the membrane of the endoplasmic reticulum. In the endoplasmic reticulum, proteins are frequently covalently modified, and oligomerize before they fold, are packaged into transport vesicles that shuttle them to the Golgi complex. Proteins that misfold in the endoplasmic reticulum are selectively transported back across the endoplasmic reticulum membrane to the cytosol for degradation by proteasomes. Depending on the topology of the defect in the protein, cytosolic or lumenal chaperones are involved in its targeting to degradation. The export channel for misfolded proteins is likely also formed by Sec61p. Export may be powered by AAA-ATPases of the proteasome 19S regulatory particle or Cdc48p/p97. Exported proteins are frequently ubiquitylated prior to degradation and are escorted to the proteasome by polyubiquitin-binding proteins.
引用
收藏
页码:435 / 456
页数:22
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