Selenium-Binding Protein 1 in Human Health and Disease

Elhodaky, Mostafa; Diamond, Alan M.

doi:10.3390/ijms19113437

Cited by 71 publications

(70 citation statements)

References 97 publications

(146 reference statements)

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“…Inversely, overexpression of GPx1 led to decreased levels of SBP1. Intriguingly, SBP1 is progressively lost during the development of many clinical tumors, which may enhance GPx1 activity (48). This observation further complicates the role of GPx1 in different stages of carcinogenesis.…”

Section: Gpx1mentioning

confidence: 99%

Regulatory Phenomena in the Glutathione Peroxidase Superfamily

Brigelius‐Flohé

Flohé

2020

Antioxidants & Redox Signaling

282

163

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Significance: The selenium-containing Glutathione peroxidases (GPxs)1-4 protect against oxidative challenge, inhibit inflammation and oxidant-induced regulated cell death. Recent Advances: GPx1 and GPx4 dampen phosphorylation cascades predominantly via prevention of inactivation of phosphatases by H 2 O 2 or lipid hydroperoxides. GPx2 regulates the balance between regeneration and apoptotic cell shedding in the intestine. It inhibits inflammation-induced carcinogenesis in the gut but promotes growth of established cancers. GPx3 deficiency facilitates platelet aggregation likely via disinhibition of thromboxane biosynthesis. It is also considered a tumor suppressor. GPx4 is expressed in three different forms. The cytosolic form proved to inhibit interleukin-1-driven nuclear factor jB activation and leukotriene biosynthesis. Moreover, it is a key regulator of ferroptosis, because it reduces hydroperoxy groups of complex lipids and silences lipoxygenases. By alternate substrate use, the nuclear form contributes to chromatin compaction. Mitochondrial GPx4 forms the mitochondrial sheath of spermatozoa and, thus, guarantees male fertility. Out of the less characterized GPxs, the cysteine-containing GPx7 and GPx8 are unique in contributing to oxidative protein folding in the endoplasmic reticulum by reacting with protein isomerase as an alternate substrate. A yeast 2-Cysteine glutathione peroxidase equipped with CP and CR was reported to sense H 2 O 2 for inducing an adaptive response. Critical Issues: Most of the findings compiled are derived from tissue culture and/or animal studies only. Their impact on human physiology is sometimes questionable. Future Directions: The expression of individual GPxs and GPx-dependent regulatory phenomena are to be further investigated, in particular in respect to human health. Antioxid. Redox Signal. 33, 498-516.

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Section: Gpx1mentioning

confidence: 99%

Regulatory Phenomena in the Glutathione Peroxidase Superfamily

Brigelius‐Flohé

Flohé

2020

Antioxidants & Redox Signaling

282

163

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“…Reduced expression of selenium-binding protein 1 (SELENBP1), since first cloned in 1997, has been frequently observed in a variety of solid tumors, and is significantly related to unfavorable clinical outcome in multiple cancer types [23]. However, the evidence concerning the clinical relevance of SELENBP1 in human bladder cancer is lacking.…”

Section: Discussionmentioning

confidence: 99%

“…Thereafter, accumulating evidence has convincingly demonstrated that reduced expression of SELENBP1 is an independent predictive of poor clinical outcome in multiple malignant diseases [13][14][15][16][17][18][20][21][22]. Furthermore, an increasing number of in vitro and in vivo studies has also consistently shown that increasing the levels of SELENBP1 significantly suppresses the malignant characteristics of cancer cells, leading scientific community to the consensus that SELENBP1 may act as a putative tumor suppressor involved in the regulation of cell proliferation, senescence, epithelial-mesenchymal transition, migration and apoptosis [23]. However, the clinical significance of SELENBP1 in human bladder cancer has not yet been characterized in any detail.…”

Section: Introductionmentioning

confidence: 99%

Selenium-binding protein 1 transcriptionally activates p21 expression via p53-independent mechanism and its frequent reduction associates with poor prognosis in bladder cancer

et al. 2020

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Background: Recent studies have shown that selenium-binding protein 1 (SELENBP1) is significantly down-regulated in a variety of solid tumors. Nevertheless, the clinical relevance of SELENBP1 in human bladder cancer has not been described in any detail, and the molecular mechanism underlying its inhibitory role in cancer cell growth is largely unknown. Methods: SELENBP1 expression levels in tumor tissues and adjacent normal tissues were evaluated using immunoblotting assay. The association of SELENBP1 expression, clinicopathological features, and clinical outcome was determined using publicly available dataset from The Cancer Genome Atlas bladder cancer (TCGA-BLCA) cohort. DNA methylation in SELENBP1 gene was assessed using online MEXPRESS tool. We generated stable SELENBP1-overexpression and their corresponding control cell lines to determine its potential effect on cell cycle and transcriptional activity of p21 by using flow cytometry and luciferase reporter assay, respectively. The dominant-negative mutant constructs, TAM67 and STAT1 Y701F, were employed to define the roles of c-Jun and STAT1 in the regulation of p21 protein. Results: Here, we report that the reduction of SELENBP1 is a frequent event and significantly correlates with tumor progression as well as unfavorable prognosis in human bladder cancer. By utilizing TCGA-BLCA cohort, DNA hypermethylation, especially in gene body, is shown to be likely to account for the reduction of SELENBP1 expression. However, an apparent paradox is observed in its 3′-UTR region, in which DNA methylation is positively related to SELENBP1 expression. More importantly, we verify the growth inhibitory role for SELENBP1 in human bladder cancer, and further report a novel function for SELENBP1 in transcriptionally modulating p21 expression through a p53-independent mechanism. Instead, ectopic expression of SELENBP1 pronouncedly attenuates the phosphorylation of c-Jun and STAT1, both of which are indispensable for SELENBP1-mediated transcriptional induction of p21, thereby resulting in the G 0 /G 1 phase cell cycle arrest in bladder cancer cell.

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“…The mechanisms by which dietary selenium may affect MM tumor progression have only been partly explored, mostly in cell lines, pointing to the crucial role of redox metabolism [ 54 ]. Although it is well established that low levels of SBP1 are frequently associated with poor clinical outcome [ 55 ], the complexity of selenium metabolism has highlighted the fact that among selenocysteine-containing proteins that are members of the glutathione peroxidase family, SBP1 is the only one for which no catalytic function has been assigned [ 56 ]. Therefore, many aspects of this research field require further investigation.…”

Section: Discussionmentioning

confidence: 99%

Cross-Species Proteomics Identifies CAPG and SBP1 as Crucial Invasiveness Biomarkers in Rat and Human Malignant Mesothelioma

Nader

Boissard

Henry

et al. 2020

Cancers

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Malignant mesothelioma (MM) still represents a devastating disease that is often detected too late, while the current effect of therapies on patient outcomes remains unsatisfactory. Invasiveness biomarkers may contribute to improving early diagnosis, prognosis, and treatment for patients, a task that could benefit from the development of high-throughput proteomics. To limit potential sources of bias when identifying such biomarkers, we conducted cross-species proteomic analyzes on three different MM sources. Data were collected firstly from two human MM cell lines, secondly from rat MM tumors of increasing invasiveness grown in immunocompetent rats and human MM tumors grown in immunodeficient mice, and thirdly from paraffin-embedded sections of patient MM tumors of the epithelioid and sarcomatoid subtypes. Our investigations identified three major invasiveness biomarkers common to the three tumor sources, CAPG, FABP4, and LAMB2, and an additional set of 25 candidate biomarkers shared by rat and patient tumors. Comparing the data to proteomic analyzes of preneoplastic and neoplastic rat mesothelial cell lines revealed the additional role of SBP1 in the carcinogenic process. These observations could provide new opportunities to identify highly vulnerable MM patients with poor survival outcomes, thereby improving the success of current and future therapeutic strategies.

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Selenium-Binding Protein 1 in Human Health and Disease

Cited by 71 publications

References 97 publications

Regulatory Phenomena in the Glutathione Peroxidase Superfamily

Regulatory Phenomena in the Glutathione Peroxidase Superfamily

Selenium-binding protein 1 transcriptionally activates p21 expression via p53-independent mechanism and its frequent reduction associates with poor prognosis in bladder cancer

Cross-Species Proteomics Identifies CAPG and SBP1 as Crucial Invasiveness Biomarkers in Rat and Human Malignant Mesothelioma

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