Overexpression of ERAP2N in Human Trophoblast Cells Promotes Cell Death

Lospinoso, Kristen; Dozmorov, Mikhail G.; Fawal, Nadine El; Raghu, Rhea; Chae, Wook‐Jin; Lee, Eun D.

doi:10.3390/ijms22168585

Cited by 6 publications

(3 citation statements)

References 41 publications

(106 reference statements)

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“…The ERAP2 SNP rs2549782 results in the isoform ERAP2N, which increases ERAP2’s affinity for hydrophobic peptides 165-fold, making the cells more susceptible to immune surveillance due to altered HLA and peptide presentations [ 90 ]. ERAP2N promotes cell death in trophoblast cells by downregulating the cell survival genes and upregulating the cell death genes [ 91 ]. ERAP2N can modulate immune recognition and potentially target cancer.…”

Section: Discussionmentioning

confidence: 99%

A Comparative Review of Pregnancy and Cancer and Their Association with Endoplasmic Reticulum Aminopeptidase 1 and 2

Hur

Wong

Lee

2023

IJMS

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The fundamental basis of pregnancy and cancer is to determine the fate of the survival or the death of humanity. However, the development of fetuses and tumors share many similarities and differences, making them two sides of the same coin. This review presents an overview of the similarities and differences between pregnancy and cancer. In addition, we will also discuss the critical roles that Endoplasmic Reticulum Aminopeptidase (ERAP) 1 and 2 may play in the immune system, cell migration, and angiogenesis, all of which are essential for fetal and tumor development. Even though the comprehensive understanding of ERAP2 lags that of ERAP1 due to the lack of an animal model, recent studies have shown that both enzymes are associated with an increased risk of several diseases, including pregnancy disorder pre-eclampsia (PE), recurrent miscarriages, and cancer. The exact mechanisms in both pregnancy and cancer need to be elucidated. Therefore, a deeper understanding of ERAP’s role in diseases can make it a potential therapeutic target for pregnancy complications and cancer and offer greater insight into its impact on the immune system.

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Section: Discussionmentioning

confidence: 99%

A Comparative Review of Pregnancy and Cancer and Their Association with Endoplasmic Reticulum Aminopeptidase 1 and 2

Hur

Wong

Lee

2023

IJMS

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“…( 32 ) found that these cells were killed by T and NK cells, and Lospinoso etal. ( 33 ) observed that such transfection caused downregulation of many genes important for cell survival, which together may explain the lack of Asn392 homozygotes in Chileans.…”

Section: Polymorphism Of Erap2 Gene—apparent Lack ...mentioning

confidence: 99%

To Be or Not to Be: The Case of Endoplasmic Reticulum Aminopeptidase 2

Kuśnierczyk

2022

Front. Immunol.

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To be, or not to be, that is the question. (William Shakespeare, Hamlet)Endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and ERAP2, respectively) play a role in trimming peptides that are too long to be bound and presented by class I HLA (HLA-I) molecules to CD8+ T cells. They may also affect the HLA-I-presented peptide repertoire by overtrimming potential epitopes. Both enzymes may also be released from the cell to cleave cytokine receptors and regulate blood pressure. Both enzymes are polymorphic, which affects their expression, specificity, and activity, resulting in their role in diseases associated with HLA-I. In this brief review, we concentrate on ERAP2, less investigated because of its lack in laboratory mice and 25% of humans, as well as a lower polymorphism. ERAP2 was found to be associated with several diseases and to influence ERAP1 effects. It was discovered recently that the defective ERAP2 gene, not encoding functional aminopeptidase, may nevertheless, during viral infections, produce a truncated protein isoform of unknown function, possibly interfering with ERAP1 and full-length ERAP2 by heterodimer formation. The disease associations of ERAP2, alone or in combination with ERAP1, are reviewed.

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“…Finally, a very topical and informative overview highlighting the role of the placenta and the use of low-dose aspirin in the prevention of pre-eclampsia [ 4 , 5 ]. In addition to the reviews, our collection also contains several novel studies covering pre-eclampsia [ 6 , 7 , 8 ]; fetal growth restriction [ 7 , 9 , 10 , 11 ]; calcium signaling [ 12 ]; placental oxidative stress, nutrition, senescence and apoptosis [ 6 , 9 , 13 , 14 , 15 ]; sexual dimorphism [ 16 , 17 , 18 ], intrahepatic cholestasis [ 19 ]; placental vascular modelling [ 20 ]; and placental villous explant culture models [ 21 ].…”

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confidence: 99%