| Title: |
Interactome Analysis of Bag-1 Isoforms Reveals Novel Interaction Partners in Endoplasmic Reticulum-Associated Degradation |
| Authors: |
Can, Nisan Denizce; Baştürk, Ezgi; Kızılboğa, Tuğba; Akçay, İzzet Mehmet; Dingiloğlu, Baran; Tatlı, Özge; Acar, Sevilay; KILBAŞ, PELİN ÖZFİLİZ; Elbeyli, Efe; Muratcioglu, Serena; Jannuzzi, Ayşe Tarbin; Gürsoy, Attila; Doğanay, Hamdi Levent; Yılmaz, Betül Karademir; Doğanay, Gizem Dinler |
| Publisher Information: |
Public Library Science |
| Publication Year: |
2021 |
| Collection: |
İstanbul Kültür Üniversitesi: OpenAccess@IKU |
| Subject Terms: |
Protein-Protein Interactions |
| 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. ; Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) Istanbul Technical University Internal Research Funds |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Plos One; 16; https://doi.org/10.1371/journal.pone.0256640; https://hdl.handle.net/11413/8232; 687944100029 |
| DOI: |
10.1371/journal.pone.0256640 |
| Availability: |
https://hdl.handle.net/11413/8232; https://doi.org/10.1371/journal.pone.0256640 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.78F2B2E1 |
| Database: |
BASE |