p53: The Multifaceted Roles of Covalent Modifications in Cancer.

The p53 protein has attracted huge research interest over several decades due to its role as one of the most important tumor suppressors in mammals, which orchestrates a synchronous response from normal cells in the body to various forms of stress. The diverse cellular activities of the p53 protein are regulated mainly via its post-translational modifications (PTMs). PTMs affect p53 on several levels: at the level of the assembly of tetrameric complexes on DNA to transactivate its target genes, at the level of the assembly of tetrameric complexes on DNA to transactivate its target genes; at the level of proteolysis in the absence of stress; and on the contrary, at the level of augmented protein stability in response to stress signals.

Lipoxygenases at the Intersection of Infection and Carcinogenesis.

The persisting presence of opportunistic pathogens like poses a significant threat to many immunocompromised cancer patients with pulmonary infections. This review highlights the complexity of interactions in the host's defensive eicosanoid signaling network and its hijacking by pathogenic bacteria to their own advantage. Human lipoxygenases (ALOXs) and their mouse counterparts are integral elements of the innate immune system, mostly operating in the pro-inflammatory mode.

Oncogenic BRCA1,2 Mutations in the Human Lineage-A By-Product of Sexual Selection?

In this review, we discuss the long-known problem of tissue-specific carcinogenesis in BRCA1 and BRCA2 mutation carriers: while the genes are expressed ubiquitously, increased cancer risk is observed mostly in the breast and ovaries, and to a much lesser extent, in some other tissues such as the prostate or pancreas. We reevaluate hypotheses on the evolutionary origin of these mutations in humans. Also, we align together the reports that at least some great apes have much lower risks of epithelial cancers in general and breast cancer in particular with the fact that humans have more voluminous breast tissue as compared to their closest extant relatives, particularly chimpanzees and bonobos.

[Investigation of oncolytic potential of vaccine strains of yellow fever and tick-borne encephalitis viruses against glioblastoma and pancreatic carcinoma cell lines].

Introduction: Flaviviruses, possessing natural neurotropicity could be used in glioblastoma therapy using attenuated strains or as a delivery system for antitumor agents in an inactivated form.

Objective: To investigate the sensitivity of glioblastoma and pancreatic carcinoma cell lines to vaccine strains of yellow fever and tick-borne encephalitis viruses.

Materials And Methods: Cell lines: glioblastoma GL-6, T98G, LN-229, pancreatic carcinoma MIA RaCa-2 and human pancreatic ductal carcinoma PANC-1.

At the Crossroads of the cGAS-cGAMP-STING Pathway and the DNA Damage Response: Implications for Cancer Progression and Treatment.

The evolutionary conserved DNA-sensing cGAS-STING innate immunity pathway represents one of the most important cytosolic DNA-sensing systems that is activated in response to viral invasion and/or damage to the integrity of the nuclear envelope. The key outcome of this pathway is the production of interferon, which subsequently stimulates the transcription of hundreds of genes. In oncology, the situation is complex because this pathway may serve either anti- or pro-oncogenic roles, depending on context.

Arachidonic acid: reconciling the dichotomy of its oxidative cascade through specific deuteration.

A new approach to attenuating pathological inflammatory reactions by buffering the eicosanoid pathways with oxidation-resistant hexadeuterated arachidonic acid (D-ARA) is discussed. Enzymatic processing of ARA, released by phospholipase A2, by lipoxygenases, cyclooxygenases, and cytochromes yields a wide range of bioactive eicosanoids, including pro-inflammation, pro-angiogenesis and pro-thrombosis species that, when produced in excess, are an underlying cause of pathology. Conversely, some products of ARA oxidation possess pro-resolving properties.

Flaviviruses in AntiTumor Therapy.

Oncolytic viruses offer a promising approach to tumor treatment. These viruses not only have a direct lytic effect on tumor cells but can also modify the tumor microenvironment and activate antitumor immunity. Due to their high pathogenicity, flaviviruses have often been overlooked as potential antitumor agents.

Non-Immunoglobulin Synthetic Binding Proteins for Oncology.

Extensive application of technologies like phage display in screening peptide and protein combinatorial libraries has not only facilitated creation of new recombinant antibodies but has also significantly enriched repertoire of the protein binders that have polypeptide scaffolds without homology to immunoglobulins. These innovative synthetic binding protein (SBP) platforms have grown in number and now encompass monobodies/adnectins, DARPins, lipocalins/anticalins, and a variety of miniproteins such as affibodies and knottins, among others. They serve as versatile modules for developing complex affinity tools that hold promise in both diagnostic and therapeutic settings.

BRCA Mutations-The Achilles Heel of Breast, Ovarian and Other Epithelial Cancers.

Two related tumor suppressor genes, and , attract a lot of attention from both fundamental and clinical points of view. Oncogenic hereditary mutations in these genes are firmly linked to the early onset of breast and ovarian cancers. However, the molecular mechanisms that drive extensive mutagenesis in these genes are not known.

Eutherian-Specific Functions of BetaM Acquired through Gene Co-Option in the Regulation of MyoD Expression.

Vertebrate genes represent a rare instance of orthologous gene co-option, resulting in radically different functions of the encoded BetaM proteins. In lower vertebrates, BetaM is a Na, K-ATPase β-subunit that is a component of ion pumps in the plasma membrane. In placental mammals, BetaM lost its ancestral role and, through structural alterations of the N-terminal domain, became a skeletal and cardiac muscle-specific protein of the inner nuclear membrane, highly expressed during late fetal and early postnatal development.

Targeting ATP12A, a Nongastric Proton Pump α Subunit, for Idiopathic Pulmonary Fibrosis Treatment.

Idiopathic pulmonary fibrosis (IPF) is a pathological condition of unknown etiology that results from injury to the lung and an ensuing fibrotic response that leads to the thickening of the alveolar walls and obliteration of the alveolar space. The pathogenesis is not clear, and there are currently no effective therapies for IPF. Small airway disease and mucus accumulation are prominent features in IPF lungs, similar to cystic fibrosis lung disease.

Role of Histone Tails and Single Strand DNA Breaks in Nucleosomal Arrest of RNA Polymerase.

Transcription through nucleosomes by RNA polymerases (RNAP) is accompanied by formation of small intranucleosomal DNA loops (i-loops). The i-loops form more efficiently in the presence of single-strand breaks or gaps in a non-template DNA strand (NT-SSBs) and induce arrest of transcribing RNAP, thus allowing detection of NT-SSBs by the enzyme. Here we examined the role of histone tails and extranucleosomal NT-SSBs in i-loop formation and arrest of RNAP during transcription of promoter-proximal region of nucleosomal DNA.

Interactome of Paraoxonase PON2 Reveals New Pathways for Tumor Growth Regulation.

The interactome of paraoxonase-2 encoded by the PON2 gene was investigated. A cDNA library was screened using a yeast two-hybrid system to search for new proteins interacting with human PON2. Analysis of the identified candidates, along with previously published data on interactors obtained by other methods, indicates the presence of a significant number of indirect interactions between PON2 and EGFR and, consequently, possible regulation of tumor growth with mutant EGFR involving PON2.

Artificial genetic polymers against human pathologies.

Originally discovered by Nielsen in 1991, peptide nucleic acids and other artificial genetic polymers have gained a lot of interest from the scientific community. Due to their unique biophysical features these artificial hybrid polymers are now being employed in various areas of theranostics (therapy and diagnostics). The current review provides an overview of their structure, principles of rational design, and biophysical features as well as highlights the areas of their successful implementation in biology and biomedicine.

Structure of an Intranucleosomal DNA Loop That Senses DNA Damage during Transcription.

Transcription through chromatin by RNA polymerase II (Pol II) is accompanied by the formation of small intranucleosomal DNA loops containing the enzyme (i-loops) that are involved in survival of core histones on the DNA and arrest of Pol II during the transcription of damaged DNA. However, the structures of i-loops have not been determined. Here, the structures of the intermediates formed during transcription through a nucleosome containing intact or damaged DNA were studied using biochemical approaches and electron microscopy.

Anti-cancer Virotherapy in Russia: Lessons from the Past, Current Challenges and Prospects for the Future.

The idea of using the lytic power of viruses against malignant cells has been entertained for many decades. However, oncolytic viruses gained broad attention as an emerging anti-cancer therapy only recently with the successful implementation of several oncolytic viruses to treat advanced melanoma. Here we review the history of oncolytic viruses in the Russian Federation and recent biotechnological advances in connection with the perspectives of their practical use against aggressive tumors such as glioblastoma or pancreatic cancer.

Deuterated Arachidonic Acid Ameliorates Lipopolysaccharide-Induced Lung Damage in Mice.

Arachidonic acid (ARA) is a major component of lipid bilayers as well as the key substrate for the eicosanoid cascades. ARA is readily oxidized, and its non-enzymatic and enzymatic oxidation products induce inflammatory responses in nearly all tissues, including lung tissues. Deuteration at bis-allylic positions substantially decreases the overall rate of ARA oxidation when hydrogen abstraction is an initiating event.

Production of Bacterial Cellulose Aerogels With Improved Physico-Mechanical Properties and Antibacterial Effect.

Aerogels have gained significant interest in recent decades because of their unique properties such as high porosity, low density, high surface area, and excellent heat and noise insulation. However, their high cost and low mechanical strength limit their practical application. We developed appropriate conditions to produce aerogels with controlled density, high mechanical strength, and thermal characteristics from bacterial cellulose (BC) synthesized by the strain H-110.

Properties of a cryptic lysyl oxidase from haloarchaeon .

Background: Lysyl oxidases (LOX) have been extensively studied in mammals, whereas properties and functions of recently found homologues in prokaryotic genomes remain enigmatic.

Methods: LOX open reading frame was cloned from in an expression vector. Recombinant lysyl oxidase (HTU-LOX) proteins were purified using metal affinity chromatography under denaturing conditions followed by refolding.

A Study of the Physical and Mechanical Properties of Aerogels Obtained from Bacterial Cellulose.

Aerogels with a density of 4.2-22.8 kg/m were obtained from bacterial cellulose synthesized under static and dynamic cultivation conditions on a molasses medium.

Expression and Intracellular Localization of Paraoxonase 2 in Different Types of Malignancies.

PON2 belongs to the paraoxonase protein family that consists of lactone hydrolyzing enzymes with different substrate specificities. Unlike other members of the family, PON2 exhibits substantial antioxidant activity, is localized predominantly inside the cell, and is ubiquitously expressed in all human tissues. Previously, it was proffered that defense against pathogens, such as , is the main function of paraoxonases.

Apoptotic Cell-Derived Extracellular Vesicles Promote Malignancy of Glioblastoma Via Intercellular Transfer of Splicing Factors.

Aggressive cancers such as glioblastoma (GBM) contain intermingled apoptotic cells adjacent to proliferating tumor cells. Nonetheless, intercellular signaling between apoptotic and surviving cancer cells remain elusive. In this study, we demonstrate that apoptotic GBM cells paradoxically promote proliferation and therapy resistance of surviving tumor cells by secreting apoptotic extracellular vesicles (apoEVs) enriched with various components of spliceosomes.

Mineralocorticoids modulate the expression of the β-3 subunit of the Na, K-ATPase in the renal collecting duct.

Renal sodium reabsorption depends on the activity of the Na,K-ATPase α/β heterodimer. Four α (α) and 3 β (β) subunit isoforms have been described. It is accepted that renal tubule cells express α/β dimers.

A strong developmental isotope effect in Caenorhabditis elegans induced by 5,5-deuterated lysine.

Effects exerted by heavy isotope substitution in biopolymers on the functioning of whole organisms have not been investigated. We report on the decrease of permissive temperature of nematodes fed with bacteria containing 5,5-D2-lysine. We synthesized 5,5-dideuterolysine and, taking advantage of lysine being an essential amino acid, showed that C.

Transcription-induced DNA supercoiling: New roles of intranucleosomal DNA loops in DNA repair and transcription.

RNA polymerase II (Pol II) transcription through chromatin is accompanied by formation of small intranucleosomal DNA loops. Pol II captured within a small loop drives accumulation of DNA supercoiling, facilitating further transcription. DNA breaks relieve supercoiling and induce Pol II arrest, allowing detection of DNA damage hidden in chromatin structure.