2022
Characterization of the AGR2 Interactome Uncovers New Players of Protein Disulfide Isomerase Network in Cancer Cells
BOUCHALOVÁ, Pavla, Lucia SOMMEROVÁ, David POTĚŠIL, Andrea MARTIŠOVÁ, Petr LAPČÍK et. al.Základní údaje
Originální název
Characterization of the AGR2 Interactome Uncovers New Players of Protein Disulfide Isomerase Network in Cancer Cells
Autoři
BOUCHALOVÁ, Pavla (203 Česká republika, domácí), Lucia SOMMEROVÁ (703 Slovensko), David POTĚŠIL (203 Česká republika, domácí), Andrea MARTIŠOVÁ (703 Slovensko, domácí), Petr LAPČÍK (203 Česká republika, domácí), Veronika BRYCHTOVÁ (203 Česká republika), Alexander SCHERL (756 Švýcarsko), Petr VOŇKA (203 Česká republika), Joan PLANAS IGLESIAS (724 Španělsko, domácí), Eric CHEVET (250 Francie), Pavel BOUCHAL (203 Česká republika, garant, domácí) a Roman HRSTKA (203 Česká republika)
Vydání
Molecular & Cellular Proteomics, American Society for Biochemistry and Molecular Biology, 2022, 1535-9484
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
10608 Biochemistry and molecular biology
Stát vydavatele
Nizozemské království
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 7.000
Kód RIV
RIV/00216224:14310/22:00125142
Organizační jednotka
Přírodovědecká fakulta
UT WoS
000750798300001
Klíčová slova anglicky
anterior gradient protein 2; protein-protein interactions; protein disulfide isomerase; mass spectrometry; secretory pathway
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 10. 10. 2024 14:52, Ing. Martina Blahová
Anotace
V originále
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.
Návaznosti
LM2018127, projekt VaV |
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MUNI/A/1604/2020, interní kód MU |
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NV19-08-00250, projekt VaV |
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90125, velká výzkumná infrastruktura |
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90127, velká výzkumná infrastruktura |
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