scholarly journals The Yin and Yang of Nrf2-Regulated Selenoproteins in Carcinogenesis

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Regina Brigelius-Flohé ◽  
Mike Müller ◽  
Doris Lippmann ◽  
Anna Patricia Kipp
Keyword(s):  
Cancer Cells ◽  
Thioredoxin Reductase ◽  
Selenium Deficiency ◽  
Related Factor ◽  
Cellular Defense ◽  
Thioredoxin Reductase 1 ◽  
Cancer Initiation ◽  
Yin And Yang ◽  
Support Tumor Growth

The NF-E2-related factor-2 (Nrf2) is a transcription factor which regulates the major cellular defense systems and thereby contributes to the prevention of many diseases including cancer. Selenium deficiency is associated with a higher cancer risk making also this essential trace element a promising candidate for cancer prevention. Two selenoproteins, thioredoxin reductase-1 (TrxR1) and glutathione peroxidase-2 (GPx2), are targets for Nrf2. Selenium deficiency activates Nrf2 as does a TrxR1 knockout making a synergism between both systems plausible. Although this might hold true for healthy cells, the interplay may turn into the opposite in cancer cells. The induction of the detoxifying and antioxidant enzymes by Nrf2 will make cancer cells chemoresistant and will protect them against oxidative damage. The essential role of TrxR1 in maintaining proliferation makes its upregulation in cancer cells detrimental. The anti-inflammatory potential of GPx2 will help to inhibit cancer initiation and inflammation-triggered promotion, but its growth supporting potential will also support tumor growth. This paper considers beneficial and adverse consequences of the activation of Nrf2 and the selenoproteins which appear to depend on the cancer stage.

scholarly journals System-wide identification and prioritization of enzyme substrates by thermal analysis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Amir Ata Saei ◽  
Christian M. Beusch ◽  
Pierre Sabatier ◽  
Juan Astorga Wells ◽  
Hassan Gharibi ◽  
...  
Keyword(s):  
Thermal Analysis ◽  
Thioredoxin Reductase ◽  
Structural Level ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Enzyme Substrate ◽  
Thioredoxin Reductase 1 ◽  
Enzyme Substrates ◽  
Substrate Proteins

AbstractDespite the immense importance of enzyme–substrate reactions, there is a lack of general and unbiased tools for identifying and prioritizing substrate proteins that are modified by the enzyme on the structural level. Here we describe a high-throughput unbiased proteomics method called System-wide Identification and prioritization of Enzyme Substrates by Thermal Analysis (SIESTA). The approach assumes that the enzymatic post-translational modification of substrate proteins is likely to change their thermal stability. In our proof-of-concept studies, SIESTA successfully identifies several known and novel substrate candidates for selenoprotein thioredoxin reductase 1, protein kinase B (AKT1) and poly-(ADP-ribose) polymerase-10 systems. Wider application of SIESTA can enhance our understanding of the role of enzymes in homeostasis and disease, opening opportunities to investigate the effect of post-translational modifications on signal transduction and facilitate drug discovery.

scholarly journals EF24 induces ROS-mediated apoptosis via targeting thioredoxin reductase 1 in gastric cancer cells

Oncotarget ◽  
2016 ◽  
Vol 7 (14) ◽  
pp. 18050-18064 ◽  
Author(s):  
Peng Zou ◽  
Yiqun Xia ◽  
Weiqian Chen ◽  
Xi Chen ◽  
Shilong Ying ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Thioredoxin Reductase ◽  
Gastric Cancer Cells ◽  
Thioredoxin Reductase 1

scholarly journals The Role of Dicentric Chromosome Formation and Secondary Centromere Deletion in the Evolution of Myeloid Malignancy

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Ruth N. MacKinnon ◽  
Lynda J. Campbell
Keyword(s):  
Cancer Cells ◽  
Genome Instability ◽  
Chromosome Organization ◽  
Myeloid Malignancy ◽  
Dicentric Chromosomes ◽  
Cancer Genomes ◽  
Cancer Initiation ◽  
Centromere Inactivation ◽  
Chromosome Formation

Dicentric chromosomes have been identified as instigators of the genome instability associated with cancer, but this instability is often resolved by one of a number of different secondary events. These include centromere inactivation, inversion, and intercentromeric deletion. Deletion or excision of one of the centromeres may be a significant occurrence in myeloid malignancy and other malignancies but has not previously been widely recognized, and our reports are the first describing centromere deletion in cancer cells. We review what is known about dicentric chromosomes and the mechanisms by which they can undergo stabilization in both constitutional and cancer genomes. The failure to identify centromere deletion in cancer cells until recently can be partly explained by the standard approaches to routine diagnostic cancer genome analysis, which do not identify centromeres in the context of chromosome organization. This hitherto hidden group of primary dicentric, secondary monocentric chromosomes, together with other unrecognized dicentric chromosomes, points to a greater role for dicentric chromosomes in cancer initiation and progression than is generally acknowledged. We present a model that predicts and explains a significant role for dicentric chromosomes in the formation of unbalanced translocations in malignancy.

scholarly journals Increased sodium selenite cytotoxicity in thioredoxin reductase 1 knockdown cancer cells

2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Ryuta Tobe ◽  
Min‐Hyuk Yoo ◽  
Noelia Fradejas‐Villar ◽  
Bradley A Carlson ◽  
Soledad Calvo ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Sodium Selenite ◽  
Thioredoxin Reductase ◽  
Thioredoxin Reductase 1
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