BAP31 interacts with Sec61 translocons and promotes retrotranslocation of CFTRΔF508 via the Derlin-1 complex
BAP31 interacts with Sec61 translocons and promotes retrotranslocation of CFTRΔF508 via the Derlin-1 complex
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DOI：
10.1016/j.cell.2008.04.042
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发表时间：
2008-06-13
期刊：
影响因子：
64.5
通讯作者：
Shore, Gordon C.
中科院分区：
文献类型：
--
作者：
Wang, Bing;Heath-Engel, Hannah;Shore, Gordon C.
BAP 31是一种内质网蛋白分选因子，与新合成的整合膜蛋白相关并控制它们的命运（即，出口、保留、存活或退化）。BAP 31本身是一种完整的膜蛋白，是几种大蛋白复合物的组成部分。在这里，我们表明，BAP 31人口的一部分相互作用的Sec 61前蛋白的两个组件，Sec 61 β和TRAM。BAP 31与其新合成的客户蛋白之一CFTR的Delta F508突变体的N末端相关联，并促进其从ER的逆易位和通过细胞质26 S蛋白酶体系统的降解。BAP 31的消耗减少了Delta F508的蛋白酶体降解，并允许显著部分的存活蛋白到达细胞表面。值得注意的是，BAP 31还在Delta F508降解途径中与Derlin-1蛋白dislocation复合物物理和功能相关。因此，BAP 31在早期步骤中操作以将新合成的CFTR Delta F508递送至其降解途径。
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, Sec61 beta and TRAM. BAP31 associates with the N terminus of one of its newly synthesized client proteins, the Delta F508 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 Delta F508 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 Delta F508 degradation pathway. Thus, BAP31 operates at early steps to deliver newly synthesized CFTR Delta F508 to its degradation pathway.