| Title | BAP31 interacts with Sec61 translocons and promotes retrotranslocation of CFTRDeltaF508 via the derlin-1 complex. | | Author(s) | Wang B, Heath-Engel H, Zhang D, Nguyen N, Thomas DY, Hanrahan JW, Shore GC | | Institution | Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Quebec, H3G 1Y6, Canada. | | Source | Cell 2008 Jun 13; 133(6):1080-92. | | MeSH | Adaptor Proteins, Signal Transducing
Animals
Cell Line
Cell-Free System
Cricetinae
Cystic Fibrosis Transmembrane Conductance Regulator
Dogs
Endoplasmic Reticulum
Humans
Membrane Proteins
Transfection
Two-Hybrid System Techniques
| | 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. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, Non-U.S. Gov't
| | PubMed ID | 18555783 |
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