Interaction of ERp57 with calreticulin: Analysis of complex formation and effects of vancomycin

Frasconi, Marco; Chichiarelli, Silvia; Gaucci, Elisa; Mazzei, Franco; Grillo, Caterina; Chinazzi, Alessandro; Altieri, Fabio

doi:10.1016/j.bpc.2011.09.003

Cited by 12 publications

(8 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The first and main function of PDIA3 is related to glycoprotein folding in the ER [9]. In fact, in association with the lectins calnexin and calreticulin, PDIA3 regulates the folding of newly synthesized cysteine-rich glycoproteins through the formation and disruption of disulfide bonds between cysteine residues [10,11]. Beyond its activity in the ER, PDIA3 plays additional functions which depend on its cellular localization.…”

Section: Introductionmentioning

confidence: 99%

PDIA3 Expression in Glioblastoma Modulates Macrophage/Microglia Pro-Tumor Activation

Chiavari¹,

Ciotti²,

Canonico

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

The glioblastoma (GB) microenvironment includes cells of the innate immune system identified as glioma-associated microglia/macrophages (GAMs) that are still poorly characterized. A potential role on the mechanisms regulating GAM activity might be played by the endoplasmic reticulum protein ERp57/PDIA3 (protein disulfide-isomerase A3), the modulation of which has been reported in a variety of cancers. Moreover, by using The Cancer Genome Atlas database, we found that overexpression of PDIA3 correlated with about 55% reduction of overall survival of glioma patients. Therefore, we analyzed the expression of ERp57/PDIA3 using specimens obtained after surgery from 18 GB patients. Immunohistochemical analysis of tumor samples revealed ERp57/PDIA3 expression in GB cells as well as in GAMs. The ERp57/PDIA3 levels were higher in GAMs than in the microglia present in the surrounding parenchyma. Therefore, we studied the role of PDIA3 modulation in microglia–glioma interaction, based on the ability of conditioned media collected from human GB cells to induce the activation of microglial cells. The results indicated that reduced PDIA3 expression/activity in GB cells significantly limited the microglia pro-tumor polarization towards the M2 phenotype and the production of pro-inflammatory factors. Our data support a role of PDIA3 expression in GB-mediated protumor activation of microglia.

show abstract

Section: Introductionmentioning

confidence: 99%

PDIA3 Expression in Glioblastoma Modulates Macrophage/Microglia Pro-Tumor Activation

Chiavari¹,

Ciotti²,

Canonico

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Additionally, it can emit vital ''immunogenic signals'' and comprise damage-associated molecular patterns (DAMPs) to activate the immune system (Garg et al, 2010;Galluzzi et al, 2012;Garg et al, 2012), which include surface-exposed calreticulin (CRT). CRT is a ubiquitous protein localized predominantly in the endoplasmic reticulum of eukaryotic cells and it plays a central role in intracellular Ca 2 þ homeostasis (Krause and Michalak, 1997;Guermonprez et al, 2003;Michalak et al, 2009;Rutkevich and Williams, 2011;Frasconi et al, 2012). CRT can also localize to the surface of some cells, such as monocytes, macrophages, neutrophils, T cells, and dendritic cells (DCs) (Cho et al, 2001;Gardai et al, 2005;Porcellini et al, 2006;Wang et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Oxidative Stress–Induced Calreticulin Expression and Translocation: New Insights into the Destruction of Melanocytes

Zhang

Liu

Jin

et al. 2014

Journal of Investigative Dermatology

View full text Add to dashboard Cite

Increased reactive oxygen species (ROS) contribute to melanocyte apoptosis and the development of cutaneous diseases or disorders via autoimmunity. However, the mechanisms and interrelationships between ROS and autoimmunity are unknown. This study aimed to investigate the role of calreticulin (CRT) in hydrogen peroxide (H2O2)-induced apoptosis in melanocytes. Total CRT levels increased in a time-dependent manner in human immortalized normal and vitiligo melanocytes exposed to H2O2-induced oxidative stress, and surface levels of CRT were increased. Moreover, CRT overexpression increased H2O2-induced apoptosis, whereas knockdown showed the opposite results. Furthermore, CRT-treated peripheral blood mononuclear cells (PBMCs) or stressed melanocytes expressed higher levels of IL-6 and tumor necrosis factor-α (TNF-α) than untreated cells (P<0.05); this effect was inhibited with CRT knockdown. In an in vivo model, CRT levels were positively correlated with lesion area (R=0.7582, P<0.0001) and duration of vitiligo in patients (P<0.001). ELISA analyses revealed that CRT expression was higher in vitiligo patients as compared with healthy subjects (P<0.05). These data demonstrate that CRT exposure via H2O2-induced oxidative stress plays a significant role in melanocyte apoptosis and suggest a relationship between apoptosis and immune reactions during melanocyte destruction.

show abstract

“…calreticulin binds the bb’ domains50 and vancomycin may hinder the interaction between calreticulin/ERp576. Other proteins interact specifically with a and/or a’ , such as REF-1/APE9 and also tapasin51.…”

Section: Discussionmentioning

confidence: 99%

“…ERp57 may also directly bind DNA, as revealed by in vitro 3 and in vivo studies4. ERp57 has been found to interact strongly with a number of small ligands, such as antibiotics56 and polyphenols7, as well as to macromolecules8910.…”

mentioning

confidence: 99%

Analysis of the interaction of calcitriol with the disulfide isomerase ERp57

Gaucci

Raimondo

Grillo

et al. 2016

Sci Rep

Self Cite

View full text Add to dashboard Cite

Calcitriol, the active form of vitamin D3, can regulate the gene expression through the binding to the nuclear receptor VDR, but it can also display nongenomic actions, acting through a membrane-associated receptor, which has been discovered as the disulfide isomerase ERp57. The aim of our research is to identify the binding sites for calcitriol in ERp57 and to analyze their interaction. We first studied the interaction through bioinformatics and fluorimetric analyses. Subsequently, we focused on two protein mutants containing the predicted interaction domains with calcitriol: abb’-ERp57, containing the first three domains, and a’-ERp57, the fourth domain only. To consolidate the achievements we used the calorimetric approach to the whole protein and its mutants. Our results allow us to hypothesize that the interaction with the a’ domain contributes to a greater extent than the other potential binding sites to the dissociation constant, calculated as a Kd of about 10−9 M.

show abstract

Interaction of ERp57 with calreticulin: Analysis of complex formation and effects of vancomycin

Cited by 12 publications

References 38 publications

PDIA3 Expression in Glioblastoma Modulates Macrophage/Microglia Pro-Tumor Activation

PDIA3 Expression in Glioblastoma Modulates Macrophage/Microglia Pro-Tumor Activation

Oxidative Stress–Induced Calreticulin Expression and Translocation: New Insights into the Destruction of Melanocytes

Analysis of the interaction of calcitriol with the disulfide isomerase ERp57

Contact Info

Product

Resources

About