Characterization of the AGR2 Interactome Uncovers New Players
of Protein Disulfide Isomerase Network in Cancer Cells

J 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

URL

Impakt faktor

Impact factor: 7.000

Kód RIV

RIV/00216224:14310/22:00125142

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1016/j.mcpro.2021.100188

UT WoS

000750798300001

Klíčová slova anglicky

anterior gradient protein 2; protein-protein interactions; protein disulfide isomerase; mass spectrometry; secretory pathway

Štítky

CF PROT, rivok

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

Název: Česká infrastruktura pro integrativní strukturní biologii (Akronym: CIISB)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Czech Infrastructure for Integrative Structural Biology

MUNI/A/1604/2020, interní kód MU

Název: Podpora biochemického výzkumu v roce 2021

Investor: Masarykova univerzita, Podpora biochemického výzkumu v roce 2021

NV19-08-00250, projekt VaV

Název: Proteotypová klasifikace renálního karcinomu ve vztahu k prognóze a terapeutické odpovědi

Investor: Ministerstvo zdravotnictví ČR, Proteotypová klasifikace renálního karcinomu ve vztahu k prognóze a terapeutické odpovědi

90125, velká výzkumná infrastruktura

Název: BBMRI-CZ III

90127, velká výzkumná infrastruktura

Název: CIISB II

Citovat

BOUCHALOVÁ, Pavla, Lucia SOMMEROVÁ, David POTĚŠIL, Andrea MARTIŠOVÁ, Petr LAPČÍK, Veronika BRYCHTOVÁ, Alexander SCHERL, Petr VOŇKA, Joan PLANAS IGLESIAS, Eric CHEVET, Pavel BOUCHAL a Roman HRSTKA. Characterization of the AGR2 Interactome Uncovers New Players of Protein Disulfide Isomerase Network in Cancer Cells. Molecular & Cellular Proteomics. American Society for Biochemistry and Molecular Biology, 2022, roč. 21, č. 2, s. 1-19. ISSN 1535-9484. Dostupné z: https://dx.doi.org/10.1016/j.mcpro.2021.100188.

@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 a 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, roč.~21, č.~2, s.~1-19. ISSN~1535-9484. Dostupné z: https://dx.doi.org/10.1016/j.mcpro.2021.100188.

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