Publication Abstract

Signal-peptide Mediated Translocation Is Regulated by a P97-AIRAPL Complex

Glinka, T., Alter, J., Braunstein, I., Tzach, L., Sheng, C. W., Geifman, S., Edelmann, M. J., Kessler, B., & Stanhill, A. (2014). Signal-peptide Mediated Translocation Is Regulated by a P97-AIRAPL Complex. Biochemical Journal. 1, 1-1. DOI:10.1042/BJ20130710.


Protein homeostasis is a fundamental requirement for all living cells in order to survive in a dynamic surrounding. Proper levels of AIRAPL (Zfand2b) are required in order to maintain cellular folding capacity in metazoan, and functional impairment of AIRAPL results in acceleration of ageing and protein aggregation. However, the cellular roles of AIRAPL in this process are not known. Here we report that AIRAPL binds and forms a complex with P97 (VCP/Cdc48), Ubxd8, Npl4-Ufd1, Derlin-1 and Bag6 on the ER membrane. In spite of the fact that AIRAPL complex partners are involved in ERAD process, AIRAPL knock-down does not show any impairment in ERAD substrate degradation. However, translocation into the ER of a subset of ERAD and non-ERAD secreted proteins, are regulated by AIRAPL. The ability to regulate translocation by the P97-AIRAPL complex is entirely dependent on the proteins signal peptide. Our results demonstrate a P97 complex regulating translocation into the ER in a signal-peptide dependent manner.