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2021 ◽  
Vol 12 (1) ◽  
Lidong Sun ◽  
Suli Lv ◽  
Tanjing Song

AbstractPrevalent dysregulation of epigenetic modifications plays a pivotal role in cancer. Targeting epigenetic abnormality is a new strategy for cancer therapy. Understanding how conventional oncogenic factors cause epigenetic abnormality is of great basic and translational value. O-GlcNAcylation is a protein modification which affects physiology and pathophysiology. In mammals, O-GlcNAcylation is catalyzed by one single enzyme OGT and removed by one single enzyme OGA. O-GlcNAcylation is affected by the availability of the donor, UDP-GlcNAc, generated by the serial enzymatic reactions in the hexoamine biogenesis pathway (HBP). O-GlcNAcylation regulates a wide spectrum of substrates including many proteins involved in epigenetic modification. Like epigenetic modifications, abnormality of O-GlcNAcylation is also common in cancer. Studies have revealed substantial impact on HBP enzymes and OGT/OGA by oncogenic signals. In this review, we will first summarize how oncogenic signals regulate HBP enzymes, OGT and OGA in cancer. We will then integrate this knowledge with the up to date understanding how O-GlcNAcylation regulates epigenetic machinery. With this, we propose a signal axis from oncogenic signals through O-GlcNAcylation dysregulation to epigenetic abnormality in cancer. Further elucidation of this axis will not only advance our understanding of cancer biology but also provide new revenues towards cancer therapy.

2021 ◽  
Yiping Wang ◽  
Malgorzata Milewska ◽  
Henry Foster ◽  
Robert Chapman ◽  
Martina H. Stenzel

2021 ◽  
Vol 11 (1) ◽  
Asta Kausaite-Minkstimiene ◽  
Algimantas Kaminskas ◽  
Anton Popov ◽  
Arunas Ramanavicius ◽  
Almira Ramanaviciene

AbstractIn this study, we reported the development of Prussian blue (PB), poly(pyrrole-2-carboxylic acid) (PPCA), and glucose oxidase (GOx) biocomposite modified graphite rod (GR) electrode as a potential biocathode for single enzyme biofuel cell fuelled by glucose. In order to design the biocathode, the GR electrode was coated with a composite of PB particles embedded in the PPCA shell and an additional layer of PPCA by cyclic voltammetry. Meanwhile, GOx molecules were covalently attached to the carboxyl groups of PPCA by an amide bond. The optimal conditions for the biocathode preparation were elaborated experimentally. After optimization, the developed biocathode showed excellent electrocatalytic activity toward the reduction of H2O2 formed during GOx catalyzed glucose oxidation at a low potential of 0.1 V vs Ag/AgCl, as well as good electrochemical performance. An electrocatalytic current density of 31.68 ± 2.70 μA/cm2 and open-circuit potential (OCP) of 293.34 ± 15.70 mV in O2-saturated 10 mM glucose solution at pH 6.0 were recorded. A maximal OCP of 430.15 ± 15.10 mV was recorded at 98.86 mM of glucose. In addition, the biocathode showed good operational stability, maintaining 95.53 ± 0.15% of the initial response after 14 days. These results suggest that this simply designed biocathode can be applied to the construction of a glucose-powered single enzyme biofuel cell.

2021 ◽  
Vol 12 (1) ◽  
Takahiro Mori ◽  
Rui Zhai ◽  
Richiro Ushimaru ◽  
Yudai Matsuda ◽  
Ikuro Abe

AbstractEndoperoxide-containing natural products are a group of compounds with structurally unique cyclized peroxide moieties. Although numerous endoperoxide-containing compounds have been isolated, the biosynthesis of the endoperoxides remains unclear. NvfI from Aspergillus novofumigatus IBT 16806 is an endoperoxidase that catalyzes the formation of fumigatonoid A in the biosynthesis of novofumigatonin. Here, we describe our structural and functional analyses of NvfI. The structural elucidation and mutagenesis studies indicate that NvfI does not utilize a tyrosyl radical in the reaction, in contrast to other characterized endoperoxidases. Further, the crystallographic analysis reveals significant conformational changes of two loops upon substrate binding, which suggests a dynamic movement of active site during the catalytic cycle. As a result, NvfI installs three oxygen atoms onto a substrate in a single enzyme turnover. Based on these results, we propose a mechanism for the NvfI-catalyzed, unique endoperoxide formation reaction to produce fumigatonoid A.

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 509
Annie Ren ◽  
Ioannis Prassas ◽  
Vijithan Sugumar ◽  
Antoninus Soosaipillai ◽  
Marcus Bernardini ◽  

Background: In this pilot study, we perform a preliminary comparison of two targeted multiplex proteomics technologies for discerning serum protein concentration changes that may correlate to tumor burden in ovarian cancer (OC) patients. Methods: Using the proximity extension assay (PEA) and Quantibody® Kiloplex Array (QKA), we measured >1,000 proteins in the pre-surgical and post-surgical serum from nine OC patients (N=18 samples). We expect that proteins that have decreased significantly in the post-surgical serum concentration may correlate to tumor burden in each patient. Duplicate sera from two healthy individuals were used as controls (N=4 samples). We employed in-house ELISAs to measure five proteins with large serum concentration changes in pre- and post-surgical sera, from four of the original nine patients and the two original controls. Results: Both platforms showed a weak correlation with clinical cancer antigen 125 (CA125) data. The two multiplexed platforms showed a significant correlation with each other for >400 overlapping proteins. PEA uncovered 15 proteins, while QKA revealed 11 proteins, with more than a two-fold post-surgical decrease in at least six of the nine patients. Validation using single enzyme-linked immunosorbent assays (ELISAs) showed at least a two-fold post-surgical decrease in serum concentration of the same patients, as indicated by the two multiplex assays. Conclusion: Both methods identified proteins that had significantly decreased in post-surgical serum concentration, as well as recognizing proteins that had been implicated in OC patients. Our findings from a limited sample size suggest that novel targeted proteomics platforms are promising tools for identifying candidate serological tumor-related proteins.  However further studies are essential for the improvement of accuracy and avoidance of false results.

2021 ◽  
Hyo Sub Choi ◽  
Ajay Bhat ◽  
Marshall B. Howington ◽  
Megan L. Schaller ◽  
Rebecca Cox ◽  

Flavin containing monooxygenases (FMOs) are promiscuous enzymes known for metabolizing a wide range of exogenous compounds. In C. elegans, fmo-2 expression increases lifespan and healthspan downstream of multiple longevity-promoting pathways through an unknown mechanism. Here, we report that, contrary to its classification as a xenobiotic enzyme, fmo-2 expression leads to rewiring of endogenous metabolism principally through changes in one carbon metabolism (OCM). Using computer modeling, we identify decreased methylation as the major OCM flux modified by FMO-2 that is sufficient to recapitulate its longevity benefits. We further find that tryptophan is decreased in multiple mammalian FMO overexpression models and is a validated substrate for FMO enzymes. Our resulting model connects a single enzyme to two previously unconnected key metabolic pathways and provides a framework for the metabolic interconnectivity of longevity-promoting pathways such as dietary restriction. FMOs are well-conserved enzymes that are also induced by lifespan-extending interventions in mice, supporting a conserved and critical role in promoting health and longevity through metabolic remodeling.

Sung Oh Woo ◽  
Myungkeun Oh ◽  
Lina Alhalhooly ◽  
Jasmin Farmakes ◽  
Arith J. Rajapakse ◽  

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