| Title: |
Interactome analysis of Bag-1 isoforms reveals novel interaction partners in endoplasmic reticulum-associated degradation |
| Authors: |
Can, Nisan Denizce; Basturk, Ezgi; Kizilboga, Tugba; Akcay, Izzet Mehmet; Dingiloglu, Baran; Tatli, Ozge; Acar, Sevilay; Kilbas, Pelin Ozfiliz; Elbeyli, Efe; Muratcioglu, Serena; Jannuzzi, Ayse Tarbin; Gursoy, Attila; Keskin, Ozlem; Doganay, Hamdi Levent; Yilmaz, Betul Karademir; Doganay, Gizem Dinler |
| Source: |
PLOS ONE 16(8) |
| Publication Year: |
2021 |
| Description: |
Bag-1 is a multifunctional protein that regulates Hsp70 chaperone activity, apoptosis, and proliferation. The three major Bag-1 isoforms have different subcellular localizations and partly non-overlapping functions. To identify the detailed interaction network of each isoform, we utilized mass spectrometry-based proteomics and found that interactomes of Bag-1 isoforms contained many common proteins, with variations in their abundances. Bag-1 interactomes were enriched with proteins involved in protein processing and degradation pathways. Novel interaction partners included VCP/p97; a transitional ER ATPase, Rad23B; a shuttling factor for ubiquitinated proteins, proteasome components, and ER-resident proteins, suggesting a role for Bag-1 also in ER-associated protein degradation (ERAD). Bag-1 pull-down from cells and tissues from breast cancer patients validated these interactions and showed cancer-related prominence. Using in silico predictions we detected hotspot residues of Bag-1. Mutations of these residues caused loss of binding to protein quality control elements and impaired proteasomal activity in MCF-7 cells. Following CD147 glycosylation pattern, we showed that Bag-1 downregulated VCP/p97-dependent ERAD. Overall, our data extends the interaction map of Bag-1, and broadens its role in protein homeostasis. Targeting the interaction surfaces revealed in this study might be an effective strategy in the treatment of cancer. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
https://aperta.ulakbim.gov.tr/record/239622; oai:aperta.ulakbim.gov.tr:239622 |
| Availability: |
https://aperta.ulakbim.gov.tr/record/239622 |
| Rights: |
info:eu-repo/semantics/openAccess ; http://www.opendefinition.org/licenses/cc-by |
| Accession Number: |
edsbas.7110439B |
| Database: |
BASE |