scholarly journals Conflicting Views on the Molecular Structure of the Cancer Antigen CA125/MUC16

2010 ◽  
Vol 28 (6) ◽  
pp. 385-394 ◽  
Author(s):  
Houda Bouanene ◽  
Abdelhédi Miled

CA125 is a tumor antigen used to monitor the progression and regression of epithelial ovarian cancer. Despite the widespread use of CA125, the biochemical and molecular nature of this antigen is poorly understood. Analysis of the structure of CA125 is essential for determining the physiological role of this very significant tumor marker. Accumulated experimental evidence has shown that CA125 epitopes reside on a molecule of very complex architecture in terms of both protein backbone and oligosaccharide structures. It is not clear whether the heterogeneity of CA125 molecular characteristics are due to the variability of biological sources from which the molecule was isolated or to the different biophysical methods used for the characterization of all the oligosaccharides linked to CA125 or to the presence of glycoisoforms for this protein. This review attempts to summarize emerging data related to molecular characteristics of CA125 and to compare approaches undertaken to reach a better understanding of molecular features of this tumor marker.

2010 ◽  
Vol 9 (1) ◽  
pp. 119 ◽  
Author(s):  
Chieko Hashizume ◽  
Hiroshi Nakano ◽  
Kimihisa Yoshida ◽  
Richard W Wong
Keyword(s):  

2016 ◽  
Vol 213 (3) ◽  
pp. 313-327 ◽  
Author(s):  
Mario Nuvolone ◽  
Mario Hermann ◽  
Silvia Sorce ◽  
Giancarlo Russo ◽  
Cinzia Tiberi ◽  
...  

Although its involvement in prion replication and neurotoxicity during transmissible spongiform encephalopathies is undisputed, the physiological role of the cellular prion protein (PrPC) remains enigmatic. A plethora of functions have been ascribed to PrPC based on phenotypes of Prnp−/− mice. However, all currently available Prnp−/− lines were generated in embryonic stem cells from the 129 strain of the laboratory mouse and mostly crossed to non-129 strains. Therefore, Prnp-linked loci polymorphic between 129 and the backcrossing strain resulted in systematic genetic confounders and led to erroneous conclusions. We used TALEN-mediated genome editing in fertilized mouse oocytes to create the Zurich-3 (ZH3) Prnp-ablated allele on a pure C57BL/6J genetic background. Genomic, transcriptional, and phenotypic characterization of PrnpZH3/ZH3 mice failed to identify phenotypes previously described in non–co-isogenic Prnp−/− mice. However, aged PrnpZH3/ZH3 mice developed a chronic demyelinating peripheral neuropathy, confirming the crucial involvement of PrPC in peripheral myelin maintenance. This new line represents a rigorous genetic resource for studying the role of PrPC in physiology and disease.


Author(s):  
Robert J. Nichols ◽  
Benjamin LaFrance ◽  
Naiya R. Phillips ◽  
Luke M. Oltrogge ◽  
Luis E. Valentin-Alvarado ◽  
...  

AbstractProkaryotic nanocompartments, also known as encapsulins, are a recently discovered proteinaceous organelle in prokaryotes that compartmentalize cargo enzymes. While initial studies have begun to elucidate the structure and physiological roles of encapsulins, bioinformatic evidence suggests that a great diversity of encapsulin nanocompartments remains unexplored. Here, we describe a novel encapsulin in the freshwater cyanobacterium Synechococcus elongatus PCC 7942. This nanocompartment is upregulated upon sulfate starvation and encapsulates a cysteine desulfurase enzyme via an N-terminal targeting sequence. Using cryoelectron microscopy, we have determined the structure of the nanocompartment complex to 2.2 Å resolution. Lastly, biochemical characterization of the complex demonstrated that the activity of the cysteine desulfurase is enhanced upon encapsulation. Taken together, our discovery, structural analysis, and enzymatic characterization of this prokaryotic nanocompartment provide a foundation for future studies seeking to understand the physiological role of this encapsulin in various bacteria.


2021 ◽  
Author(s):  
Qiaofeng Zhang ◽  
Furong Liu ◽  
Lu Qin ◽  
Zhibin Liao ◽  
Jia Song ◽  
...  

Abstract Background: Gastrointestinal adenocarcinoma (GIAD) has caused a serious disease burden globally. Targeted therapy for the transforming growth factor beta (TGF-β) signaling pathway is becoming a reality. However, the molecular characterization of TGF-β in GIAD requires further exploration.Results: The TGF-β­­high group had a worse prognosis in overall GIAD patients, and had a worse prognosis trend in gastric cancer and colon cancer specifically. Signatures (including mRNA and proteins) of the TGF-β­­high group is highly correlated with EMT. According to miRNA analysis, miR-215-3p, miR-378a-5p, and miR-194-3p may block the effect of TGF-β. Further genomic analysis showed that TGF-β­­low group had more genomic changes in gastric cancer, such as TP53 mutation, EGFR amplification, and SMAD4 deletion. And drug response dataset revealed sensitive drugs or drug resistant drugs corresponding to TGF-β associated mRNAs. Finally, the DNN model showed an excellent predictive effect in predicting TGF-β status in different GIAD datasets.Conclusions: Our study provided a comprehensive analysis of the molecular characteristics associated with TGF-β and provides possible therapeutic targets in GIAD.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Alyssa Imbert ◽  
Magali Rompais ◽  
Mohammed Selloum ◽  
Florence Castelli ◽  
Emmanuelle Mouton-Barbosa ◽  
...  

AbstractGenes are pleiotropic and getting a better knowledge of their function requires a comprehensive characterization of their mutants. Here, we generated multi-level data combining phenomic, proteomic and metabolomic acquisitions from plasma and liver tissues of two C57BL/6 N mouse models lacking the Lat (linker for activation of T cells) and the Mx2 (MX dynamin-like GTPase 2) genes, respectively. Our dataset consists of 9 assays (1 preclinical, 2 proteomics and 6 metabolomics) generated with a fully non-targeted and standardized approach. The data and processing code are publicly available in the ProMetIS R package to ensure accessibility, interoperability, and reusability. The dataset thus provides unique molecular information about the physiological role of the Lat and Mx2 genes. Furthermore, the protocols described herein can be easily extended to a larger number of individuals and tissues. Finally, this resource will be of great interest to develop new bioinformatic and biostatistic methods for multi-omics data integration.


1999 ◽  
Vol 181 (15) ◽  
pp. 4592-4597 ◽  
Author(s):  
Jeffrey A. Pederson ◽  
Gerald J. Mileski ◽  
Bart C. Weimer ◽  
James L. Steele

ABSTRACT A cell envelope-associated proteinase gene (prtH) was identified in Lactobacillus helveticus CNRZ32. TheprtH gene encodes a protein of 1,849 amino acids and with a predicted molecular mass of 204 kDa. The deduced amino acid sequence of the prtH product has significant identity (45%) to that of the lactococcal PrtP proteinases. Southern blot analysis indicates thatprtH is not broadly distributed within L. helveticus. A prtH deletion mutant of CNRZ32 was constructed to evaluate the physiological role of PrtH. PrtH is not required for rapid growth or fast acid production in milk by CNRZ32. Cell surface proteinase activity and specificity were determined by hydrolysis of αs1-casein fragment 1-23 by whole cells. A comparison of CNRZ32 and its prtH deletion mutant indicates that CNRZ32 has at least two cell surface proteinases that differ in substrate specificity.


1997 ◽  
Vol 272 (5) ◽  
pp. G994-G999 ◽  
Author(s):  
I. Depoortere ◽  
T. L. Peeters

This is the first report on central motilin receptors. Autoradiography on cerebellar slices revealed specific motilin-binding sites in the molecular layer of the cortex. Scatchard analysis of cold saturation studies showed the existence of a high-(pKd,hi = 9.07 +/- 0.09, where pKd is the negative logarithm of the dissociation constant) and a low-affinity binding site (pKd,lo = 6.56 +/- 0.09). Similar affinities were found with rabbit motilin and with the porcine (po) antagonist [Phe3, Leu13]po-motilin. Feline and canine motilin had a markedly lower affinity for the low-affinity site (pKd,lo = 5.29 and 4.58, respectively); chicken motilin had a lower affinity for both sites (pKd,hi = 8.36, pKd,lo = 3.97). Erythromycin A and its derivative N-trimethyl erythromycin A cnol ether also bound to cerebellar motilin receptors (pKd,hi = 7.29 and 8.91, respectively). Structure-activity studies with motilin fragments and the potency ranking of agonists suggest that a novel subtype receptor of motilin may exist in the brain. Guanosine 5'-O-(3-thiotriphosphate) (0.1 mM) reduced the number and the affinity for the high-affinity binding sites, which is evidence for G protein-coupled receptors. Our findings open new perspectives for the study of the physiological role of motilin.


2006 ◽  
Vol 72 (1) ◽  
pp. 233-238 ◽  
Author(s):  
Ronnie Machielsen ◽  
Agustinus R. Uria ◽  
Servé W. M. Kengen ◽  
John van der Oost

ABSTRACT The gene encoding a novel alcohol dehydrogenase that belongs to the aldo-keto reductase superfamily has been identified in the hyperthermophilic archaeon Pyrococcus furiosus. The gene, referred to as adhD, was functionally expressed in Escherichia coli and subsequently purified to homogeneity. The enzyme has a monomeric conformation with a molecular mass of 32 kDa. The catalytic activity of the enzyme increases up to 100°C, and a half-life value of 130 min at this temperature indicates its high thermostability. AdhD exhibits a broad substrate specificity with, in general, a preference for the reduction of ketones (pH optimum, 6.1) and the oxidation of secondary alcohols (pH optimum, 8.8). Maximal specific activities were detected with 2,3-butanediol (108.3 U/mg) and diacetyl-acetoin (22.5 U/mg) in the oxidative and reductive reactions, respectively. Gas chromatrography analysis indicated that AdhD produced mainly (S)-2-pentanol (enantiomeric excess, 89%) when 2-pentanone was used as substrate. The physiological role of AdhD is discussed.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 13 ◽  
Author(s):  
Veljko Veljkovic ◽  
Vladimir Perovic ◽  
Marko Anderluh ◽  
Slobodan Paessler ◽  
Milena Veljkovic ◽  
...  

Background: Healthy nutrition is vital for good health and well-being. Despite the important role of a healthy nutritional diet, recommendations for healthy eating remain elusive and are mainly based on general properties of nutrients. The present study proposes an improved characterization of the molecular characteristics of nutrients, which are important for biological functions and can be useful in describing a healthy diet. Methods: We investigated the electronic properties of some known nutrient ingredients. In this analysis, we used the average quasi valence number (AQVN) and the electron-ion interaction potential (EIIP), which are molecular descriptors that represent the basic electronic properties of organic molecules.  Results: Our results show that most nutrients can be represented by specific groups of organic compounds according to their basic electronic properties, and these differ from the vast majority of known chemicals. Based on this finding, we have proposed a simple criterion for the selection of food components for healthy nutrition. Discussion: Further studies on the electronic properties of nutrients could serve as a basis for better understanding of their biological functions.


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