Oxidation of peroxiredoxin-4 induces oligomerization and promotes interaction with proteins governing protein folding and endoplasmic reticulum stress

Elko, Evan; Manuel, Allison M.; White, Sheryl L.; Zito, Ester; Vliet, Albert van der; Anathy, Vikas; Janssen–Heininger, Yvonne M. W.

doi:10.1016/j.jbc.2021.100665

Cited by 19 publications

(13 citation statements)

References 46 publications

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“…Indeed, GSN functions as an actin-modulating protein and plays a role in tumorigenesis, invasion, and migration. In addition to physiological functions, PRDX4 is also involved in therapeutic resistance, metastasis, and recurrence of tumors; its high expression is associated with the depth of invasion, lymph node metastasis, and short survival time [32,33]. Noteworthily, this study is the first to determine the roles of GSN and PRDX4 in the migration and invasion of CRC and tumor growth in nude mice xenograft models of cancer.…”

Section: Proteomic Profiling Of the Lymph Node Metastasized Colorecta...mentioning

confidence: 91%

2D-DIGE-MS Proteomics Approaches for Identification of Gelsolin and Peroxiredoxin 4 with Lymph Node Metastasis in Colorectal Cancer

Huang

Lee

Tung

et al. 2022

Cancers

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Background/Aims: A combination of fluorescence two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry approach was used to search for potential markers for prognosis and intervention of colorectal cancer (CRC) at different stages of lymph node metastasis (LMN). This quantitative proteomic survey aimed to investigate the LNM-associated proteins and evaluate the clinicopathological characteristics of these target proteins in CRC from stage I to stage IV. Methods: Sixteen CRC cases were categorized into paired non-LNM and LNM groups, and two-dimensional difference gel electrophoresis and MS proteome analysis were performed. Differential protein expression between non-LNM and LNM CRC was further validated in a tissue microarray, including 40 paraffin-embedded samples by immunohistochemistry staining. Moreover, a Boyden chamber assay, flow cytometry, and shRNA were used to examine the epithelial–mesenchymal transition and mechanism invasiveness of the differentially expressed proteins in DLD-1 cells and in vivo xenograft mouse model. Results: Eighteen differentially expressed proteins were found between non-LNM and LNM CRC tissues. Among them, protein levels of Gelsolin (GSN) and peroxiredoxin 4 (PRDX4) were abundant in node-positive CRC. Downregulation of GSN and PRDX4 markedly suppressed migration and invasiveness and also induced cell cycle G1/S arrest in DLD-1. Mechanistically, the EGFR/RhoA/PKCα/ERK pathways are critical for transcriptional activation of histone modification of H3 lysine 4 trimethylation (H3K4me3) of GSN and PRDX4 promoters, resulting in upregulation of GSN, PRDX4, Twist-1/2, cyclinD1, proliferating cell-nuclear antigen, β-catenin, N-cadherin, and matrix metalloprotein-9. Conclusions: GSN and PRDX4 are novel regulators in CRC lymph node metastasis to potentially provide new insights into the mechanism of CRC progression and serve as a biomarker for CRC diagnosis at the metastatic stage.

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Section: Proteomic Profiling Of the Lymph Node Metastasized Colorecta...mentioning

confidence: 91%

2D-DIGE-MS Proteomics Approaches for Identification of Gelsolin and Peroxiredoxin 4 with Lymph Node Metastasis in Colorectal Cancer

Huang

Lee

Tung

et al. 2022

Cancers

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“…These aggregates are presented by decamers or dodecamers formed by dimers via hydrophobic interactions or disulfide bonds, though these bonds are not essential for stabilizing the aggregates [ 110 ]. Formation of high molecular weight structures has been shown for Prdx1 [ 111 ], Prdx2 [ 112 ], Prdx3 [ 106 ], Prdx4 [ 20 , 113 ], and Prdx6 [ 114 ]. Aggregation is promoted by heat shock [ 115 ] and various posttranslational modifications, including peroxidation [ 113 , 116 ], phosphorylation of tyrosine residues [ 117 ], lysine acetylation [ 118 ], and nitrosylation [ 119 ].…”

Section: Peroxiredoxins As Regulatory Proteinsmentioning

confidence: 99%

Peroxiredoxins—The Underrated Actors during Virus-Induced Oxidative Stress

et al. 2021

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Enhanced production of reactive oxygen species (ROS) triggered by various stimuli, including viral infections, has attributed much attention in the past years. It has been shown that different viruses that cause acute or chronic diseases induce oxidative stress in infected cells and dysregulate antioxidant its antioxidant capacity. However, most studies focused on catalase and superoxide dismutases, whereas a family of peroxiredoxins (Prdx), the most effective peroxide scavengers, were given little or no attention. In the current review, we demonstrate that peroxiredoxins scavenge hydrogen and organic peroxides at their physiological concentrations at various cell compartments, unlike many other antioxidant enzymes, and discuss their recycling. We also provide data on the regulation of their expression by various transcription factors, as they can be compared with the imprint of viruses on transcriptional machinery. Next, we discuss the involvement of peroxiredoxins in transferring signals from ROS on specific proteins by promoting the oxidation of target cysteine groups, as well as briefly demonstrate evidence of nonenzymatic, chaperone, functions of Prdx. Finally, we give an account of the current state of research of peroxiredoxins for various viruses. These data clearly show that Prdx have not been given proper attention despite all the achievements in general redox biology.

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“…Single-cell profiling has been used to examine the gene expression programs activated during 3D breast epithelial acinar morphogenesis [36]. The global analysis identifies JUND transcription factor, as well as a transcript cluster containing genes that have strong connection with oxidative stress responses and ER stress (SLC25A28 [37], BCL2L13 [38], FAF2 [39], PRDX4 [40], FAM120A [41], SERP1 [42], and FOXO1). SLC25A28, a mitochondrial iron importer, was reported to mediate metabolic reprograming in tumorigenesis [37].…”

Section: Metabolic Regulators Heterogeneously Activated In 3d Mcf10a Spheroidsmentioning

confidence: 99%

“…PRDX4 is the only PRDX (peroxiredoxins) family member located within the ER. Overoxidation of PRDX4 acts as inducers of the UPR and ER oxidative stress [40]. SERP1 is a γ-secretase activator in the cells experiencing ER stress [42].…”

Section: Metabolic Regulators Heterogeneously Activated In 3d Mcf10a Spheroidsmentioning

confidence: 99%

Metabolic Stress Adaptations Underlie Mammary Gland Morphogenesis and Breast Cancer Progression

Wang

2021

Cells

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Breast cancers display dynamic reprogrammed metabolic activities as cancers develop from premalignant lesions to primary tumors, and then metastasize. Numerous advances focus on how tumors develop pro-proliferative metabolic signaling that differs them from adjacent, non-transformed epithelial tissues. This leads to targetable oncogene-driven liabilities among breast cancer subtypes. Other advances demonstrate how microenvironments trigger stress-response at single-cell resolution. Microenvironmental heterogeneities give rise to cell regulatory states in cancer cell spheroids in three-dimensional cultures and at stratified terminal end buds during mammary gland morphogenesis, where stress and survival signaling juxtapose. The cell-state specificity in stress signaling networks recapture metabolic evolution during cancer progression. Understanding lineage-specific metabolic phenotypes in experimental models is useful for gaining a deeper understanding of subtype-selective breast cancer metabolism.

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Oxidation of peroxiredoxin-4 induces oligomerization and promotes interaction with proteins governing protein folding and endoplasmic reticulum stress

Cited by 19 publications

References 46 publications

2D-DIGE-MS Proteomics Approaches for Identification of Gelsolin and Peroxiredoxin 4 with Lymph Node Metastasis in Colorectal Cancer

2D-DIGE-MS Proteomics Approaches for Identification of Gelsolin and Peroxiredoxin 4 with Lymph Node Metastasis in Colorectal Cancer

Peroxiredoxins—The Underrated Actors during Virus-Induced Oxidative Stress

Metabolic Stress Adaptations Underlie Mammary Gland Morphogenesis and Breast Cancer Progression

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