2. Academic Validation
  3. Interactome analysis of Bag-1 isoforms reveals novel interaction partners in endoplasmic reticulum-associated degradation

Interactome analysis of Bag-1 isoforms reveals novel interaction partners in endoplasmic reticulum-associated degradation

  • PLoS One. 2021 Aug 24;16(8):e0256640. doi: 10.1371/journal.pone.0256640.
Nisan Denizce Can 1,  Ezgi Basturk 1,  Tugba Kizilboga 1,  Izzet Mehmet Akcay 1,  Baran Dingiloglu 1,  Ozge Tatli 1 2,  Sevilay Acar 1,  Pelin Ozfiliz Kilbas 1 3,  Efe Elbeyli 4,  Serena Muratcioglu 4,  Ayse Tarbin Jannuzzi 5,  Attila Gursoy 4,  Ozlem Keskin 4,  Hamdi Levent Doganay 6,  Betul Karademir Yilmaz 7,  Gizem Dinler Doganay 1
Affiliations

Affiliations

  • 1 Department of Molecular Biology-Genetics and Biotechnology, Istanbul Technical University, Istanbul, Turkey.
  • 2 Molecular Biology and Genetics Department, Istanbul Medeniyet University, Istanbul, Turkey.
  • 3 Department of Molecular Biology and Genetics, Istanbul Kultur University, Istanbul, Turkey.
  • 4 Department of Chemical and Biological Engineering, Koc University, Istanbul, Turkey.
  • 5 Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Istanbul University, Istanbul, Turkey.
  • 6 GLAB, Umraniye Teaching and Research Hospital, Istanbul, Turkey.
  • 7 Department of Biochemistry, School of Medicine/Genetic and Metabolic Diseases Research and Investigation Center, Marmara University, Istanbul, Turkey.
PMID: 34428256 DOI: 10.1371/journal.pone.0256640
Abstract

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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12861
    99.90%, p97 AAA ATPase/VCP抑制剂
    p97
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