BAP31与Sec61转运体相互作用，并通过derlin-1复合体促进CFTRDeltaF508的逆向转运。

BAP31 interacts with Sec61 translocons and promotes retrotranslocation of CFTRDeltaF508 via the derlin-1 complex.

作者信息

Wang Bing, Heath-Engel Hannah, Zhang Donglei, Nguyen Nhi, Thomas David Y, Hanrahan John W, Shore Gordon C

机构信息

Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Quebec, H3G 1Y6, Canada.

出版信息

Cell. 2008 Jun 13;133(6):1080-92. doi: 10.1016/j.cell.2008.04.042.

DOI:10.1016/j.cell.2008.04.042

PMID:18555783

Abstract

BAP31 is an endoplasmic reticulum protein-sorting factor that associates with newly synthesized integral membrane proteins and controls their fate (i.e., egress, retention, survival, or degradation). BAP31 is itself an integral membrane protein and a constituent of several large protein complexes. Here, we show that a part of the BAP31 population interacts with two components of the Sec61 preprotein translocon, Sec61beta and TRAM. BAP31 associates with the N terminus of one of its newly synthesized client proteins, the DeltaF508 mutant of CFTR, and promotes its retrotranslocation from the ER and degradation by the cytoplasmic 26S proteasome system. Depletion of BAP31 reduces the proteasomal degradation of DeltaF508 and permits a significant fraction of the surviving protein to reach the cell surface. Of note, BAP31 also associates physically and functionally with the Derlin-1 protein disclocation complex in the DeltaF508 degradation pathway. Thus, BAP31 operates at early steps to deliver newly synthesized CFTRDeltaF508 to its degradation pathway.

摘要

BAP31是一种内质网蛋白质分选因子，它与新合成的整合膜蛋白结合并控制其命运（即输出、保留、存活或降解）。BAP31本身是一种整合膜蛋白，也是几种大型蛋白质复合物的组成成分。在此，我们发现一部分BAP31群体与Sec61前体蛋白转运体的两个组分Sec61β和TRAM相互作用。BAP31与其新合成的一种客户蛋白（CFTR的ΔF508突变体）的N端结合，并促进其从内质网的逆向转运以及被细胞质26S蛋白酶体系统降解。BAP31的缺失会减少ΔF508的蛋白酶体降解，并使相当一部分存活的蛋白到达细胞表面。值得注意的是，在ΔF508降解途径中，BAP31还在物理和功能上与Derlin-１蛋白错位复合物相关联。因此，BAP31在早期步骤发挥作用，将新合成的CFTRΔF508输送到其降解途径。