Signal-peptide-mediated translocation is regulated by a p97-AIRAPL complex
| Autor: | Lolita Tzach, Chia Wei Sheng, Mariola J. Edelmann, Ariel Stanhill, Ilana Braunstein, Tal Glinka, Benedikt M. Kessler, Joel Alter, Susana Geifman |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Signal peptide
Cell Cycle Proteins Chromosomal translocation Protein Sorting Signals Protein aggregation Endoplasmic-reticulum-associated protein degradation Biology Endoplasmic Reticulum Biochemistry Mice Ubiquitin Valosin Containing Protein Animals Humans Molecular Biology Adaptor Proteins Signal Transducing Adenosine Triphosphatases Gene knockdown Endoplasmic reticulum Cell Membrane RNA-Binding Proteins Zinc Fingers Cell Biology Cell biology Protein Transport biology.protein Carrier Proteins Homeostasis Protein Binding |
| Popis: | Protein homoeostasis is a fundamental requirement for all living cells in order to survive in a dynamic surrounding. Proper levels of AIRAPL (arsenite-inducible RNA-associated protein-like protein) (ZFAND2B) are required in order to maintain cellular folding capacity in metazoans, and functional impairment of AIRAPL results in acceleration of aging and protein aggregation. However, the cellular roles of AIRAPL in this process are not known. In the present paper, we report that AIRAPL binds and forms a complex with p97 [VCP (valosin-containing protein)/Cdc48], Ubxd8 (ubiquitin regulatory X domain 8), Npl4–Ufd1, Derlin-1 and Bag6 on the ER (endoplasmic reticulum) membrane. In spite of the fact that AIRAPL complex partners are involved in the ERAD (ER-associated degradation) process, AIRAPL knockdown 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. |
| Databáze: | OpenAIRE |
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