Other formats:
BibTeX
LaTeX
RIS
@article{1817657,
author = {Bouchalová, Pavla and Sommerová, Lucia and Potěšil, David and Martišová, Andrea and Lapčík, Petr and Brychtová, Veronika and Scherl, Alexander and Voňka, Petr and Planas Iglesias, Joan and Chevet, Eric and Bouchal, Pavel and Hrstka, Roman},
article_number = {2},
doi = {http://dx.doi.org/10.1016/j.mcpro.2021.100188},
keywords = {anterior gradient protein 2; protein-protein interactions; protein disulfide isomerase; mass spectrometry; secretory pathway},
language = {eng},
issn = {1535-9484},
journal = {Molecular & Cellular Proteomics},
title = {Characterization of the AGR2 Interactome Uncovers New Players of Protein Disulfide Isomerase Network in Cancer Cells},
url = {https://www.sciencedirect.com/science/article/pii/S1535947621001602?via%3Dihub},
volume = {21},
year = {2022}
}
TY - JOUR
ID - 1817657
AU - Bouchalová, Pavla - Sommerová, Lucia - Potěšil, David - Martišová, Andrea - Lapčík, Petr - Brychtová, Veronika - Scherl, Alexander - Voňka, Petr - Planas Iglesias, Joan - Chevet, Eric - Bouchal, Pavel - Hrstka, Roman
PY - 2022
TI - Characterization of the AGR2 Interactome Uncovers New Players of Protein Disulfide Isomerase Network in Cancer Cells
JF - Molecular & Cellular Proteomics
VL - 21
IS - 2
SP - 1-19
EP - 1-19
PB - American Society for Biochemistry and Molecular Biology
SN - 15359484
KW - anterior gradient protein 2
KW - protein-protein interactions
KW - protein disulfide isomerase
KW - mass spectrometry
KW - secretory pathway
UR - https://www.sciencedirect.com/science/article/pii/S1535947621001602?via%3Dihub
N2 - AGR2 is an endoplasmic reticulum (ER)-resident protein disulfide isomerase (PDI) known to be overexpressed in many human epithelial cancers, and is involved in cell migration, cellular transformation, angiogenesis, and metastasis. This protein inhibits the activity of the tumor suppressor p53 and its expression levels can be used to predict cancer patient outcome. However, the precise network of AGR2-interacting partners and clients remains to be fully characterized. Herein, we used label-free quantification and also SILAC-based LC-MS/MS analyses to identify proteins interacting with AGR2. Functional annotation confirmed that AGR2 and its interaction partners are associated with processes in the ER that maintain intracellular metabolic homeostasis and participate in the unfolded protein response, including those associated with changes in cellular metabolism, energy, and redox states in response to ER stress. As a proof of concept, the interaction between AGR2 and PDIA3, another ER resident PDI, was studied in more detail. Pathway analysis revealed that AGR2 and PDIA3 play roles in protein folding in ER, including posttranslational modification and in cellular response to stress. We confirmed the AGR2-PDIA3 complex formation in cancer cells, which was enhanced in response to ER stress. Accordingly, molecular docking characterized potential quaternary structure of this complex, however, it remains to be elucidated whether (i) AGR2 rather contributes to PDIA3 maturation in ER, (ii) the complex directly acts in cellular signaling, or (iii) mediates AGR2 secretion. Our study provides a comprehensive insight into the protein-protein interaction network of AGR2 by identifying functionally relevant proteins and related cellular and biochemical pathways associated with the role of AGR2 in cancer cells.
ER -
BOUCHALOVÁ, Pavla, Lucia SOMMEROVÁ, David POTĚŠIL, Andrea MARTIŠOVÁ, Petr LAPČÍK, Veronika BRYCHTOVÁ, Alexander SCHERL, Petr VOŇKA, Joan PLANAS IGLESIAS, Eric CHEVET, Pavel BOUCHAL and Roman HRSTKA. Characterization of the AGR2 Interactome Uncovers New Players of Protein Disulfide Isomerase Network in Cancer Cells. \textit{Molecular \&{} Cellular Proteomics}. American Society for Biochemistry and Molecular Biology, 2022, vol.~21, No~2, p.~1-19. ISSN~1535-9484. Available from: https://dx.doi.org/10.1016/j.mcpro.2021.100188.
|
