AGR2, ERp57/GRP58, and some other human protein disulfide isomerases

Shishkin, S. S.; Eremina, L. S.; Ковалев, Л. И.; Kovaleva, M. A.

doi:10.1134/s000629791313004x

Cited by 29 publications

(23 citation statements)

References 129 publications

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“…Therefore, through bioinformatics analysis and molecular biology validation, we found that miR‐3647‐5p can target the 3′UTR of AGR2 and inhibit the expression of AGR2. AGR2 is a protein disulfide isomerase . Studies have found that compared to normal pancreatic tissues, the expression of AGR2 is up‐regulated in benign pancreatic lesions, low‐grade and high‐grade tumors .…”

Section: Discussionmentioning

confidence: 99%

TP53 mediated miR‐3647‐5p prevents progression of cervical carcinoma by targeting AGR2

et al. 2019

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Previous studies have shown that miRNAs involved in a number of biological processes, such as cell growth, development, differentiation, and apoptosis. The dysregulation of miRNA expression is associated with various diseases, including cervical cancer. However, the involvement of miR‐3647‐5p in the progression of tumors is unclear. In this study, we confirmed that miR‐3647‐5p was down‐regulated during cervical carcinogenesis and development, which was positively correlated with the prognosis of patients with cervical cancer. In addition, our study showed that miR‐3647‐5p can inhibit the proliferation of cervical cancer cells and promote apoptosis, suggesting that miR‐3647‐5p is involved in the development of cervical cancer as a tumor suppressor gene. Furthermore, we found that transcription factor TP53 could promote the expression of miR‐3647‐5p, suggesting that the dysfunction of miR‐3647‐5p in cervical cancer may be related to TP53. In addition, we also found that miR‐3647‐5p can inhibit the proliferation of cervical cancer cells and promote apoptosis by targeting AGR2. In summary, our research reveals that transcription factor TP53 promotes the expression of miR‐3647‐5p, while up‐regulated miR‐3647‐5p targets AGR2, inhibiting cervical cancer cell proliferation and promoting apoptosis. Our study reveals the mechanism of TP53/miR‐3647‐5p/AGR2 axis in cervical cancer, which may be useful for targeted therapy of cervical cancer.

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Section: Discussionmentioning

confidence: 99%

TP53 mediated miR‐3647‐5p prevents progression of cervical carcinoma by targeting AGR2

et al. 2019

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“…AGR2, also known as PDIA17, XAG‐2, hAG‐2, an ER‐resident protein mainly expressed in human epithelial cells, was assigned to the human Protein Disulphide Isomerase (PDI) family later than all other members [Shishkin et al., ]. The PDI family has 21 proteins that are involved in numerous physiological and pathological processes [Shishkin et al., ]. PDI proteins have an important structural feature in common, one or several thioredoxin‐like domains and also similar intracellular localisation – in the ER and/or in other membrane formations.…”

Section: Agr2 and The Tnsmentioning

confidence: 99%

The role of protein disulphide isomerase AGR2 in the tumour niche

Delom

Nazaraliyev

Fessart

2018

Biology of the Cell

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In recent years, the discovery of 'tumour niche', a microenvironment that favours tumour development has changed our perspective of cancer. This microenvironment generated by the tumour cells itself and surrounding cells is capable of providing essential elements for its growth. Consequently, the homoeostasis of the secretory pathway (SP) has become an essential player in cancer development. The SP not only promotes cellular adaptation to protein misfolding due to oncogenic transformation or challenging tumour niche but also allows tumour cells to produce specific secretomes. This impacts tumour cells in cis-or trans-as well as stromal cells in the tumour niche. In this context, the Anterior GRadient 2 (AGR2) protein has been identified as a key player. AGR2 is a protein disulphide isomerase that resides in the endoplasmic reticulum (ER) and mediates the formation of disulphide bonds, catalyses the cysteine-based redox reactions and assists the quality control of proteins. AGR2 not only plays an essential role in the homoeostasis of the SP but also exerts pro-oncogenic gain-of-function due to its reported mislocalisation in the tumour niche microenvironment. In this review, we summarise the dual role of AGR2, inside and outside the ER, on the tumour niche and its microenvironment.

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“…ERp57 is a member of the protein disulfide isomerase family that is mainly located in the endoplasmic reticulum, and has well-characterized functions as a cellular protective protein [ 31 , 32 , 53 ]. It participates in the quality control of newly synthesized glycoproteins, in association with calnexin/calreticulin, and is also an important component of the major histocompatibility complex class I peptide loading complex [ 53 – 55 ].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, we focused the present study on investigating the ability of LEDGF/p75 to protect PCa cells against oxidative stress-induced necrosis, and contribute to the upregulation of endoplasmic reticulum protein of 57 kD (ERp57) in PCa. ERp57, also known as glucose regulated protein of 58 kD (GRP58) and protein disulfide isomerase family A member 3 (PDIA3), is a multi-functional thiol-oxidoreductase and a chaperone protein responsible for maintaining the appropriate folding of newly synthetized glycoproteins [ 31 , 32 ]. Our results indicate that LEDGF/p75 overexpression attenuates oxidative stress-induced necrotic cell death and contributes to ERp57 upregulation in the context of PCa.…”

Section: Introductionmentioning

confidence: 99%

LEDGF/p75 Overexpression Attenuates Oxidative Stress-Induced Necrosis and Upregulates the Oxidoreductase ERP57/PDIA3/GRP58 in Prostate Cancer

et al. 2016

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Prostate cancer (PCa) mortality is driven by highly aggressive tumors characterized by metastasis and resistance to therapy, and this aggressiveness is mediated by numerous factors, including activation of stress survival pathways in the pro-inflammatory tumor microenvironment. LEDGF/p75, also known as the DFS70 autoantigen, is a stress transcription co-activator implicated in cancer, HIV-AIDS, and autoimmunity. This protein is targeted by autoantibodies in certain subsets of patients with PCa and inflammatory conditions, as well as in some apparently healthy individuals. LEDGF/p75 is overexpressed in PCa and other cancers, and promotes resistance to chemotherapy-induced cell death via the transactivation of survival proteins. We report in this study that overexpression of LEDGF/p75 in PCa cells attenuates oxidative stress-induced necrosis but not staurosporine-induced apoptosis. This finding was consistent with the observation that while LEDGF/p75 was robustly cleaved in apoptotic cells into a p65 fragment that lacks stress survival activity, it remained relatively intact in necrotic cells. Overexpression of LEDGF/p75 in PCa cells led to the upregulation of transcript and protein levels of the thiol-oxidoreductase ERp57 (also known as GRP58 and PDIA3), whereas its depletion led to ERp57 transcript downregulation. Chromatin immunoprecipitation and transcription reporter assays showed LEDGF/p75 binding to and transactivating the ERp57 promoter, respectively. Immunohistochemical analysis revealed significantly elevated co-expression of these two proteins in clinical prostate tumor tissues. Our results suggest that LEDGF/p75 is not an inhibitor of apoptosis but rather an antagonist of oxidative stress-induced necrosis, and that its overexpression in PCa leads to ERp57 upregulation. These findings are of significance in clarifying the role of the LEDGF/p75 stress survival pathway in PCa.

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AGR2, ERp57/GRP58, and some other human protein disulfide isomerases

Cited by 29 publications

References 129 publications

TP53 mediated miR‐3647‐5p prevents progression of cervical carcinoma by targeting AGR2

TP53 mediated miR‐3647‐5p prevents progression of cervical carcinoma by targeting AGR2

The role of protein disulphide isomerase AGR2 in the tumour niche

LEDGF/p75 Overexpression Attenuates Oxidative Stress-Induced Necrosis and Upregulates the Oxidoreductase ERP57/PDIA3/GRP58 in Prostate Cancer

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