A5066539568- Phosphodiesterase function and regulation
- DNA Repair Mechanisms
- PARP inhibition in cancer therapy
- Cancer, Hypoxia, and Metabolism
- Mitochondrial Function and Pathology
- Peptidase Inhibition and Analysis
- Microtubule and mitosis dynamics
- RNA modifications and cancer
- Inflammatory mediators and NSAID effects
- Medicinal plant effects and applications
- Cancer Mechanisms and Therapy
- Radiation Therapy and Dosimetry
- ATP Synthase and ATPases Research
- Cancer therapeutics and mechanisms
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- CRISPR and Genetic Engineering
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Toxoplasma gondii Research Studies
- Sirtuins and Resveratrol in Medicine
- Multiple Myeloma Research and Treatments
- Endometriosis Research and Treatment
- Synthesis and biological activity
- MicroRNA in disease regulation
- Neonatal Respiratory Health Research
University of South Alabama
2015-2024
USA Mitchell Cancer Institute
2015-2024
Cancer Research Institute
2013
Abstract Changes in nicotinamide adenine dinucleotide (NAD + ) levels that compromise mitochondrial function trigger release of DNA damaging reactive oxygen species. NAD also affect repair capacity as is a substrate for PARP-enzymes (mono/poly-ADP-ribosylation) and sirtuins (deacetylation). The ecto-5′-nucleotidase CD73, an ectoenzyme highly expressed cancer, suggested to regulate intracellular by processing its bio-precursor, mononucleotide (NMN), from tumor microenvironments, thereby...
Human respiratory syncytial virus (RSV), a major cause of severe diseases, efficiently suppresses cellular innate immunity, represented by type I interferon (IFN), using its two unique nonstructural proteins, NS1 and NS2. In search for their mechanism, was previously shown to decrease levels TRAF3 IKKε, whereas NS2 interacted with RIG-I decreased STAT2. Here, we report on the interaction, localization, functional domains these proteins. We show that recombinant NS2, expressed in lung...
Previously, miR-345 was identified as one of the most significantly downregulated microRNAs in pancreatic cancer (PC); however, its functional significance remained unexplored. overexpressed PC cells by stable transfection, and effect on growth, apoptosis mitochondrial-membrane potential examined WST-1, Hoechst-33342/Annexin-V, JC-1 staining, respectively. Gene expression quantitative reverse-transcription-PCR and/or immunoblotting, subcellular fractions prepared caspase-3/7 activity...
Assembly and disassembly of DNA repair protein complexes at damage sites are essential for maintaining genomic integrity. Investigating factors coordinating assembly the base excision (BER) proteins polymerase β (Polβ) XRCC1 to lesion identifies a role Polβ in regulating from and, conversely, demonstrates Polβ's dependence on complex assembly. LivePAR, genetically encoded probe live-cell imaging poly(ADP-ribose) (PAR), reveals that require PAR repair-complex assembly, with PARP1 PARP2...
Protein syntheses mediated by cellular and viral internal ribosome entry sites (IRESs) are believed to have many features in common. Distinct mechanisms for recruitment preinitiation complex assembly between the two processes not been identified thus far. Here we show that methylation status of rRNA differentially influenced mechanism 80S formation on IRES elements from sodium-coupled neutral amino acid transporter 2 (SNAT2) versus hepatitis C virus mRNA. Translation initiation involves 48S...
// Arun Bhardwaj 1, * , Sanjeev K. Srivastava Seema Singh 1 Sumit Arora Nikhil Tyagi Joel Andrews Steven McClellan James E. Carter 2 Ajay P. 3 Department of Oncologic Sciences, Mitchell Cancer Institute, University South Alabama, Mobile, USA Pathology, College Medicine, Biochemistry and Molecular Biology, Authors contributed equally in this manuscript Correspondence to: Singh, e-mail: asingh@health.southalabama.edu Keywords: CXCL12/CXCR4, docetaxel, microtubules, PAK4, LIMK1 Received: August...
// Kevin Lee 1 , Ashley S. Lindsey Nan Li 2 Bernard Gary Joel Andrews 3 Adam B. Keeton A. Piazza Drug Discovery Research Center, Mitchell Cancer Institute, University of South Alabama, Mobile, USA Department Biochemistry and Molecular Genetics, The Alabama at Birmingham, Correspondence to: Lee, e-mail: kjlee@health.southalabama.edu Keywords: β-catenin, PKG, PKA, PDE10A, colon cancer Received: September 09, 2015 Accepted: December 07, Published: 21, 2015 ABSTRACT...
Argonaute (Ago) plays a central role in RNA interference metazoans, but its status lower organisms remains ill-defined. We report on the Ago complex of unicellular protozoan, Toxoplasma gondii (Tg), an obligatory pathogen mammalian hosts. The PIWI-like domain TgAgo lacked canonical DDE/H catalytic triad, explaining weak target cleavage activity. However, associated with stronger slicer, Tudor staphylococcal nuclease (TSN), and protein Arg methyl transferase, PRMT1. Mutational analysis...
Abstract Although the role of ErbB2/HER2 oncogene in cancers has been extensively studied, how ErbB2 is regulated remains poorly understood. A novel microRNA, mir-4728, was recently found within an intron gene. However, function and clinical relevance this intronic miRNA are completely unknown. Here, we demonstrate that mir-4728 a negative regulator MAPK signaling through directly targeting ERK upstream kinase MST4 exerts numerous tumor-suppressive properties vitro animal models....
DNA repair defects have been increasingly focused on as therapeutic targets. In hormone-positive breast cancer, XRCC1-deficient tumors identified and proposed targets for combination therapies that damage inhibit pathways. XRCC1 is a scaffold protein functions in base excision (BER) by mediating essential interactions between glycosylases, AP endonuclease, poly(ADP-ribose) polymerase 1, β (POL β), ligases. Loss of confers BER hypersensitivity to damaging agents. not evaluated triple negative...
Abstract Protein–protein interactions regulate many essential enzymatic processes in the cell. Somatic mutations outside of an enzyme active site can therefore impact cellular function by disruption critical protein–protein interactions. In our investigation T304I cancer mutation DNA Polymerase β (Polβ), we find that this surface threonine residue impacts Polβ We show proteasome-mediated degradation is regulated both ubiquitin-dependent and ubiquitin-independent via unique The proteasome...
Abstract Elevated expression of the DNA damage response proteins PARP1 and poly(ADP-ribose) glycohydrolase (PARG) in glioma stem cells (GSCs) suggests that may be a unique target for PARG inhibitors (PARGi). While PARGi-induced cell death is achieved when combined with ionizing radiation, as single agent appear to mostly cytostatic. Supplementation NAD+ precursor dihydronicotinamide riboside (NRH) rapidly increased levels GSCs cells, inducing activation mild suppression replication fork...
Highly coordinated DNA repair pathways exist to detect, excise and replace damaged bases, coordinate of strand breaks. While molecular biology techniques have clarified structure, enzymatic functions, kinetics proteins, there is still a need understand how within the nucleus. Laser micro-irradiation offers powerful tool for inducing damage monitoring recruitment proteins. Induction by laser can occur with range wavelengths, users reliably induce single breaks, base lesions double breaks...
Dihydroxyacetone phosphate (DHAP) is the endogenous byproduct of fructose metabolism. Excess DHAP in cells can induce advanced glycation end products and oxidative stress. (DHA) triose precursor to DHAP. DHA used as active ingredient sunless tanning products, including aerosolized spray tans, formed by combustion solvents found electronic cigarettes. Human exposure has been increasing popularity cigarettes grown. Topically applied absorbed through viable layers skin into bloodstream....
A leading theory for ovarian carcinogenesis proposes that inflammation associated with incessant ovulation is a driver of oncogenesis. Consistent this theory, nonsteroidal anti-inflammatory drugs (NSAIDs) exert promising chemopreventive activity cancer. Unfortunately, toxicity long-term use NSAIDs due to their cyclooxygenase (COX) inhibitory activity. Previous studies suggest the antineoplastic COX independent, and rather may be exerted through phosphodiesterase (PDE) inhibition. PDEs...
Bisphenol A (BPA) is used heavily in the production of polycarbonate plastics, thermal receipt paper, and epoxies. Ubiquitous exposure to BPA has been linked obesity, diabetes, breast reproductive system cancers. Resistance chemotherapeutic agents also shown cancer cell models. Here, we investigated BPA's ability confer resistance camptothecin (CPT) mouse embryonic fibroblasts (MEFs). MEFs are sensitive CPT; however, co-exposure with CPT improved survival. Co-exposure significantly reduced...
Abstract Previous studies have reported that phosphodiesterase 10A (PDE10) is overexpressed in colon epithelium during early stages of tumorigenesis and essential for cancer cell growth. Here we describe a novel non-COX inhibitory derivative the anti-inflammatory drug, sulindac, with selective PDE10 activity, ADT 061. 061 potently inhibited growth cells expressing high levels PDE10, but not normal colonocytes do express PDE10. The concentration range by which was identical to concentrations...
SummaryDNA has been isolated from γ-irradiated yeast cells and then treated with the enzyme S1 nuclease. This cleaves DNA specifically at sites where localized denaturation occurred can therefore be used as a lesion probe to identify regions in base-pairing disrupted. By analysing number of single strand breaks, double breaks alkali-labile before after treatment nuclease, it possible calculate nuclease-sensitive induced result exposure ionizing radiation. These were found occur frequency...
Fostriecin is a natural product purified from Sterptomyces extracts with antitumor activity sufficient to warrant human clinical trials. Unfortunately, difficulties associated supply and stable drug formulation stalled further development. At molecular level, fostriecin known act as catalytic inhibitor of four PPP-family phosphatases, reports describing the design molecules in this class suggest derivatives targeting enzymes within fostriecin-sensitive subfamily can be successful. However,...
Pseudomonas aeruginosa is a Gram-negative, opportunistic pathogen that causes nosocomial pneumonia, urinary tract infections, and bacteremia. A hallmark of P. pathogenesis disruption host cell function by the type III secretion system (T3SS) its cognate exoenzyme effectors.
Mutations in isocitrate dehydrogenase isoform 1 (IDH1) are primarily found secondary glioblastoma (GBM) and low-grade glioma but rare primary GBM. The standard treatment for GBM includes radiation combined with temozolomide, an alkylating agent. Fortunately, IDH1 mutant gliomas sensitive to this treatment, resulting a more favorable prognosis. However, it's estimated that up 75 % of will progress WHO grade IV over time develop resistance agents. Therefore, understanding the mechanism(s) by...
In contrast to prokaryotes, the precise mechanism of incorporation ribosomal proteins into ribosomes in eukaryotes is not well understood. For majority eukaryotic proteins, residues critical for rRNA binding, a key step hierarchical assembly ribosomes, have been defined. this study, we used mammalian protein L13a as model investigate mechanism(s) underlying ribosomes. This work identified arginine residue at position 68 being essential binding and We also demonstrated that takes place during...