A5038867835- Phosphodiesterase function and regulation
- Microtubule and mitosis dynamics
- Respiratory viral infections research
- Peptidase Inhibition and Analysis
- interferon and immune responses
- Medicinal plant effects and applications
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Signaling Pathways in Disease
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Animal Virus Infections Studies
- MicroRNA in disease regulation
- Inflammatory mediators and NSAID effects
- Cancer Mechanisms and Therapy
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Cellular transport and secretion
- Cancer therapeutics and mechanisms
- Heat shock proteins research
- Toxin Mechanisms and Immunotoxins
- Asthma and respiratory diseases
- Angiogenesis and VEGF in Cancer
- RNA modifications and cancer
- Viral Infections and Vectors
- RNA Research and Splicing
University of South Alabama
2011-2023
USA Mitchell Cancer Institute
2017-2023
D.F. Chebotarev Institute of Gerontology
2019
National Academy of Medical Sciences of Ukraine
2019
Cancer Research Institute
2013
University of Alberta
2013
ABSTRACT The two nonstructural (NS) proteins NS1 and NS2 of respiratory syncytial virus (RSV) are abundantly expressed in the infected cell but not packaged mature progeny virions. We found that both were early infection, whereas cells underwent apoptosis much later. Coincident with NS protein expression, a number cellular antiapoptotic factors or activated at stages, which included NF-κB phosphorylated forms kinases AKT, phosphoinositide-dependent kinase, glycogen synthase kinase. Using...
ABSTRACT Viruses of the Paramyxoviridae family, such as respiratory syncytial virus (RSV), suppress cellular innate immunity represented by type I interferon (IFN) for optimal growth in their hosts. The two unique n on s tructural (NS) proteins, NS1 and NS2, RSV IFN synthesis, well function, but exact targets are still uncharacterized. Here, we investigate if either or both NS proteins affect steady-state levels key members pathway. We found that NS2 decreased TRAF3, a strategic integrator...
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...
The naturally occurring benzoquinone ansamycin compound, geldanamycin (GA), is a specific inhibitor of heat shock protein 90 (Hsp90) and potential anticancer agent. Since Plasmodium falciparum has been reported to have an Hsp90 ortholog, we tested the possibility that GA might inhibit it thereby display antiparasitic activity. We provide direct recombinant DNA evidence for falciparum, causative agent fatal malaria. While mRNA was mainly expressed in ring trophozoite stages, found all...
We previously showed that ribosomal protein L13a is required for translational silencing of gamma interferon (IFN-gamma)-induced ceruloplasmin (Cp) synthesis in monocytes. This also requires the presence GAIT (IFN-gamma activated inhibitor translation) element 3' untranslated region (UTR) Cp mRNA. Considering an inflammatory protein, we hypothesized this mechanism may have evolved to silence a family proinflammatory proteins, which just one member. To identify other mRNAs are targets...
Transient, repetitive occlusion stimulates coronary collateral growth (CCG) in normal animals. Vascular smooth muscle cells (VSMCs) switch to synthetic phenotype early CCG, then return contractile phenotype. CCG is impaired the metabolic syndrome. We determined whether was attributable aberrant VSMC phenotypic modulation by miR-145-mediated mechanisms, and restoration of physiological miR-145 levels syndrome (JCR rat) improved CCG.CCG stimulated transient, left anterior descending artery...
Reversible protein phosphorylation is relatively unexplored in the intracellular protozoa of Apicomplexa family that includes genus Plasmodium, to which belong causative agents malaria. Members PP1 represent most highly conserved phosphatase sequences phylogeny and play essential regulatory roles various cellular pathways. Previous evidence suggested a PP1-like activity Plasmodium falciparum, not yet identified at molecular level. We have catalytic subunit from P. falciparum named it PfPP1....
Immunophilins are protein chaperones with peptidylprolyl isomerase activity that belong to one of two large families, the cyclosporin-binding cyclophilins (CyPs) and FK506-binding proteins (FKBPs). Each family displays characteristic conserved sequence features differ between families. We report a novel group dual-family immunophilins contain both CyP FKBP domains for which we propose name FCBP (FK506- protein). The Toxoplasma gondii, protozoan parasite, contained N-terminal C-terminal...
ABSTRACT The La antigen (SS-B) associates with a wide variety of cellular and viral RNAs to affect gene expression in multiple systems. We show that is the major protein found be associated abundant 44-nucleotide leader RNA (leRNA) early after infection respiratory syncytial virus (RSV), nonsegmented negative-strand virus. Consistent this, redistributes from nucleus cytoplasm RSV-infected cells. Upon interference knockdown La, leRNA redirected associate RNA-binding RIG-I, known activator...
Respiratory syncytial virus (RSV) is the foremost respiratory pathogen in newborns and claims millions of lives annually. However, there has been no methodical study pathway(s) entry RSV or its interaction with nonrespiratory tissues. We others have recently established a significant association between allergic conjunctivitis presence eye. Here we adopt BALB/c mouse model demonstrate that when instilled live murine eye, not only replicated robustly eye but also migrated to lung produced...
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...
Genetic germline variants of PPP2R5D (encoding: phosphoprotein phosphatase 2 regulatory protein 5D) result in PPP2R5D-related disorder (Jordan's Syndrome), which is characterized by intellectual disability, hypotonia, seizures, macrocephaly, autism spectrum disorder, and delayed motor skill development. The originates from de novo single nucleotide mutations, generating missense that act a dominant manner. Pathogenic mutations altering 13 different amino acids have been identified, with the...
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...
As obligatory parasites, viruses co-opt a variety of cellular functions for robust replication. The expression the nonsegmented negative-strand RNA genome respiratory syncytial virus (RSV), significant pediatric pathogen, absolutely requires actin and is stimulated by actin-regulatory protein profilin. major contractile protein, it was important to determine whether known functional domains profilin were their ability activate RSV transcription. Analyses recombinant mutants in reconstituted...
We have previously shown that transient coronary artery occlusion stimulated collateral growth (CCG) in healthy (Sprague Dawley) but not metabolic syndrome (JCR:LA-cp [JCR] ) rats. Here, we sought to determine whether matrix metalloproteinases (MMPs) negatively regulate CCG the via release of endostatin and angiostatin.Rats underwent transient, repetitive left anterior descending resultant myocardial ischemia (RI) for 0 10 days. was measured collateral-dependent normal zones using...
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...
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,...
Intrinsically disordered regions (IDR) and short linear motifs (SLiMs) play pivotal roles in the intricate signaling networks governed by phosphatases kinases. B56δ (encoded PPP2R5D ) is a regulatory subunit of protein phosphatase 2A (PP2A) with long IDRs that harbor substrate-mimicking SLiM multiple phosphorylation sites. De novo missense mutations cause intellectual disabilities (ID), macrocephaly, Parkinsonism, broad range neurological symptoms. Our single-particle cryo-EM structures...