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https://www.readbyqxmd.com/read/28717196/trib1-is-a-positive-regulator-of-hepatocyte-nuclear-factor-4-alpha
#1
Sébastien Soubeyrand, Amy Martinuk, Ruth McPherson
The TRIB1 locus has been linked to both cardiovascular disease and hepatic steatosis. Recent efforts have revealed TRIB1 to be a major regulator of liver function, largely, but not exclusively, via CEBPA degradation. We recently uncovered a functional interaction between TRIB1 and HNF4A, another key regulator of hepatic function, whose molecular underpinnings remained to be clarified. Here we have extended these findings. In hepatoma models, HNF4A levels were found to depend on TRIB1, independently of its impact on CEBPA...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716987/control-of-pathological-cardiac-hypertrophy-by-transcriptional-corepressor-irf2bp2-interferon-regulatory-factor-2-binding-protein-2
#2
Jing Fang, Tianyu Li, Xuehai Zhu, Ke-Qiong Deng, Yan-Xiao Ji, Chun Fang, Xiao-Jing Zhang, Jun-Hong Guo, Peng Zhang, Hongliang Li, Xiang Wei
The transcription factor nuclear factor of activated T-cells 1 (NFAT1), with the aid of transcriptional coactivators, has been recognized for its necessity and sufficiency to drive pathological cardiac hypertrophy. However, how the transcriptional activity of NFAT1 in terms of cardiac hypertrophy is controlled at the transcriptional level has not been well defined. Herein, we showed that a cardiac-enriched protein IRF2BP2 (interferon regulatory factor-2 binding protein 2) was further upregulated in both human and mouse hypertrophied myocardium and negatively regulated cardiomyocyte hypertrophic response in vitro...
July 17, 2017: Hypertension
https://www.readbyqxmd.com/read/28716827/galectin-1-driven-tolerogenic-programs-aggravate-yersinia-enterocolitica-infection-by-repressing-antibacterial-immunity
#3
Roberto C Davicino, Santiago P Méndez-Huergo, Ricardo J Eliçabe, Juan C Stupirski, Ingo Autenrieth, María S Di Genaro, Gabriel A Rabinovich
Yersinia enterocolitica is an enteropathogenic bacterium that causes gastrointestinal disorders, as well as extraintestinal manifestations. To subvert the host's immune response, Y. enterocolitica uses a type III secretion system consisting of an injectisome and effector proteins, called Yersinia outer proteins (Yops), that modulate activation, signaling, and survival of immune cells. In this article, we show that galectin-1 (Gal-1), an immunoregulatory lectin widely expressed in mucosal tissues, contributes to Y...
July 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28716409/from-experiment-driven-database-analyses-to-database-driven-experiments-in-arabidopsis-thaliana-transcription-factor-research
#4
REVIEW
Reinhard Hehl
Experiment-driven database analysis is employed in forward genetics to predict the function of genes assocíated with a mutant phenotype. These analyses subsequently lead to database-driven experiments involving reverse genetics to verify functional predictions based on bioinformatic analyses. Genomic transcription factors (TFs) are key regulators of gene expression by binding to short regulatory sequences and by interacting with other TFs. Currently more than 2400 TFs are predicted for A. thaliana. As DNA-binding proteins they are particularly amenable to database-driven experiments, especially when their binding site specificities are known...
September 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28715808/retinoic-acid-facilitates-toll-like-receptor-4-expression-to-improve-intestinal-barrier-function-through-retinoic-acid-receptor-beta
#5
Yingying Li, Yuan Gao, Ting Cui, Ting Yang, Lan Liu, Tingyu Li, Jie Chen
BACKGROUND/AIMS: Vitamin A (VA) protects the intestinal epithelial barrier by improving cell migration and proliferation. Our previous studies demonstrated that VA deficiency (VAD) during pregnancy suppresses the systemic and mucosal immune responses in the intestines of offspring and that VA supplementation (VAS) during early life can increase immune cell counts. However, little is known about the mechanisms by which VA regulates intestinal epithelial barrier function. METHODS: Caco-2 cells were treated with all-trans retinoic acid (ATRA) for 24 hours to determine the optimum ATRA concentration to which the cells in question respond...
July 17, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28715655/macrophage-exosomes-as-natural-nanocarriers-for-protein-delivery-to-inflamed-brain
#6
Dongfen Yuan, Yuling Zhao, William A Banks, Kristin M Bullock, Matthew Haney, Elena Batrakova, Alexander V Kabanov
Recent work has stimulated interest in the use of exosomes as nanocarriers for delivery of small drugs, RNAs, and proteins to the central nervous system (CNS). To overcome the blood-brain barrier (BBB), exosomes were modified with brain homing peptides that target brain endothelium but likely to increase immune response. Here for the first time we demonstrate that there is no need for such modification to penetrate the BBB in mammals. The naïve macrophage (Mϕ) exosomes can utilize, 1) on the one hand, the integrin lymphocyte function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1), and, 2) on the other hand, the carbohydrate-binding C-type lectin receptors, to interact with brain microvessel endothelial cells comprising the BBB...
July 10, 2017: Biomaterials
https://www.readbyqxmd.com/read/28715423/antibody-trapping-a-novel-mechanism-of-parasite-immune-evasion-by-the-trematode-echinostoma-caproni
#7
Alba Cortés, Javier Sotillo, Carla Muñoz-Antolí, Javier Molina-Durán, J Guillermo Esteban, Rafael Toledo
BACKGROUND: Helminth infections are among the most prevalent neglected tropical diseases, causing an enormous impact in global health and the socioeconomic growth of developing countries. In this context, the study of helminth biology, with emphasis on host-parasite interactions, appears as a promising approach for developing new tools to prevent and control these infections. METHODS/PRINCIPAL FINDINGS: The role that antibody responses have on helminth infections is still not well understood...
July 17, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28715419/the-t-cell-leukemia-related-rpl10-r98s-mutant-traps-the-60s-export-adapter-nmd3-in-the-ribosomal-p-site-in-yeast
#8
Stephanie Patchett, Sharmishtha Musalgaonkar, Andrey G Malyutin, Arlen W Johnson
Mutations in the ribosomal protein Rpl10 (uL16) can be drivers of T-cell acute lymphoblastic leukemia (T-ALL). We previously showed that these T-ALL mutations disrupt late cytoplasmic maturation of the 60S ribosomal subunit, blocking the release of the trans-acting factors Nmd3 and Tif6 in S. cerevisiae. Consequently, these mutant ribosomes do not efficiently pass the cytoplasmic quality control checkpoint and are blocked from engaging in translation. Here, we characterize suppressing mutations of the T-ALL-related rpl10-R98S mutant that bypass this block and show that the molecular defect of rpl10-R98S is a failure to release Nmd3 from the P site...
July 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28715177/ribosome-mediated-quinary-interactions-modulate-in-cell-protein-activities
#9
Christopher M DeMott, Subhabrata Majumder, David S Burz, Sergey Reverdatto, Alexander Shekhtman
Ribosomes are present inside bacterial cells at micromolar concentrations and occupy up to 20% of the cell volume. Under these conditions even weak quinary interactions between ribosomes and cytosolic proteins can affect protein activity. By using in-cell and in vitro NMR spectroscopy, and biophysical techniques, we show that the enzymes, adenylate kinase and dihydrofolate reductase, and the respective co-enzymes, ATP and NADPH, bind to ribosomes with micromolar affinity, and that this interaction suppresses the enzymatic activities of both enzymes...
July 17, 2017: Biochemistry
https://www.readbyqxmd.com/read/28714960/bin1-reverses-pd-l1-mediated-immune-escape-by-inactivating-the-c-myc-and-egfr-mapk-signaling-pathways-in-non-small-cell-lung-cancer
#10
J Wang, Y Jia, S Zhao, X Zhang, X Wang, X Han, Y Wang, M Ma, J Shi, L Liu
Non-small cell lung cancer (NSCLC) is one of the most common and malignant carcinoma worldwide, and the incidence and mortality are increasing rapidly. Immunotherapy targeting programmed death 1/programmed death ligand 1 (PD-L1) signaling has shown prominent clinical effects in treating NSCLC; however, a poor understanding of the associated regulating molecular mechanisms of PD-L1 has become one of the biggest obstacles for further improving efficacy. Bridging integrator-1 (BIN1) can regulate numerous cancer-related molecules to exert multiple tumor-suppressing effects by either interacting or not interacting with c-MYC...
July 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28714556/non-canonical-activation-of-histidine-kinase-kdpd-by-phosphotransferase-protein-ptsn-through-interaction-with-the-transmitter-domain
#11
Markus Mörk-Mörkenstein, Ralf Heermann, Yvonne Göpel, Kirsten Jung, Boris Görke
The two-component system KdpD/KdpE governs K(+) homeostasis by controlling synthesis of the high affinity K(+) transporter KdpFABC. When sensing low environmental K(+) concentrations, the dimeric kinase KdpD autophosphorylates in trans and transfers the phosphoryl-group to the response regulator KdpE, which subsequently activates kdpFABC transcription. In Escherichia coli, KdpD can also be activated by interaction with the non-phosphorylated form of the accessory protein PtsN. PtsN stimulates KdpD kinase activity thereby increasing phospho-KdpE levels...
July 17, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28714474/facultative-ctcf-sites-moderate-mammary-super-enhancer-activity-and-regulate-juxtaposed-gene-in-non-mammary-cells
#12
M Willi, K H Yoo, F Reinisch, T M Kuhns, H K Lee, C Wang, L Hennighausen
Precise spatiotemporal gene regulation is paramount for the establishment and maintenance of cell-specific programmes. Although there is evidence that chromatin neighbourhoods, formed by the zinc-finger protein CTCF, can sequester enhancers and their target genes, there is limited in vivo evidence for CTCF demarcating super-enhancers and preventing cross talk between distinct regulatory elements. Here, we address these questions in the Wap locus with its mammary-specific super-enhancer separated by CTCF sites from widely expressed genes...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28713917/stim1-silencing-inhibits-the-migration-and-invasion-of-a549-cells
#13
Yadong Wang, Haiyu Wang, Teng Pan, Li Li, Jiangmin Li, Haiyan Yang
The present study aimed to explore the effects of stromal interaction molecule 1 (STIM1) knockdown on the migration, invasion and metastasis of A549 cells in vitro and in vivo. Western blotting and immunohistochemistry were used to detect protein expression levels. Wound healing and Transwell invasion assays were used to assess the migratory and invasive abilities of A549 cells transfected with STIM1‑specific short hairpin (sh)RNA (shSTIM1). In addition, a tail vein metastatic assay was performed. The results demonstrated that the frequency of STIM1 high‑expression was significantly increased in metastatic lung cancer tissues (72...
July 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713569/kctd12-modulation-of-gaba-b-receptor-function
#14
Melody Li, Carol J Milligan, Haiyan Wang, Andrew Walker, Leonid Churilov, Andrew J Lawrence, Christopher A Reid, Seth C Hopkins, Steven Petrou
The molecular composition and functional diversity of native GABAB receptors (GABABR) are still poorly understood, thus hindering development of selective GABABR ligands. Potassium channel tetramerization domain-containing protein (KCTD) 12 is a GABABR auxiliary subunit and mouse KCTD12 can alter GABABR function. In this study, we sought to characterize the effects of human KCTD12 on GABABR kinetics and pharmacology, using an automated electrophysiological assay. Seizure susceptibility and ethanol consumption were also investigated in a KCTD12 knockout mouse model...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28713337/the-s-layer-associated-serine-protease-homolog-prtx-impacts-cell-surface-mediated-microbe-host-interactions-of-lactobacillus-acidophilus-ncfm
#15
Brant R Johnson, Sarah O'Flaherty, Yong Jun Goh, Ian Carroll, Rodolphe Barrangou, Todd R Klaenhammer
Health-promoting aspects attributed to probiotic microorganisms, including adhesion to intestinal epithelia and modulation of the host mucosal immune system, are mediated by proteins found on the bacterial cell surface. Notably, certain probiotic and commensal bacteria contain a surface (S-) layer as the outermost stratum of the cell wall. S-layers are non-covalently bound semi-porous, crystalline arrays of self-assembling, proteinaceous subunits called S-layer proteins (SLPs). Recent evidence has shown that multiple proteins are non-covalently co-localized within the S-layer, designated S-layer associated proteins (SLAPs)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28713250/impaired-in-vivo-gamma-oscillations-in-the-medial-entorhinal-cortex-of-knock-in-alzheimer-model
#16
Tomoaki Nakazono, Travis N Lam, Ayushi Y Patel, Masashi Kitazawa, Takashi Saito, Takaomi C Saido, Kei M Igarashi
The entorhinal cortex (EC) has bidirectional connections with the hippocampus and plays a critical role in memory formation and retrieval. EC is one of the most vulnerable regions in the brain in early stages of Alzheimer's disease (AD), a neurodegenerative disease with progressive memory impairments. Accumulating evidence from healthy behaving animals indicates gamma oscillations (30-100 Hz) as critical for mediating interactions in the circuit between EC and hippocampus. However, it is still unclear whether gamma oscillations have causal relationship with memory impairment in AD...
2017: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/28712573/ve-cadherin-phosphorylation-regulates-endothelial-fluid-shear-stress-responses-through-the-polarity-protein-lgn
#17
Daniel E Conway, Brian G Coon, Madhusuthan Budatha, Paul T Arsenovic, Fabrizio Orsenigo, Florian Wessel, Jiasheng Zhang, Zhenwu Zhuang, Elisabetta Dejana, Dietmar Vestweber, Martin A Schwartz
Fluid shear stress due to blood flow on the vascular endothelium regulates blood vessel development, remodeling, physiology, and pathology [1, 2]. A complex consisting of PECAM-1, VE-cadherin, and vascular endothelial growth factor receptors (VEGFRs) that resides at endothelial cell-cell junctions transduces signals important for flow-dependent vasodilation, blood vessel remodeling, and atherosclerosis. PECAM-1 transduces forces to activate src family kinases (SFKs), which phosphorylate and transactivate VEGFRs [3-5]...
July 10, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28710641/a-ligand-binding-assay-to-measure-the-affinity-and-specificity-of-sterol-binding-proteins-in-vitro
#18
Rabih Darwiche, Roger Schneiter
Sterols are major constituents of the plasma membrane of eukaryotic cells and serve as a precursor for several classes of signaling molecules, including steroids and hydroxy sterols. They maintain the functionality and permeability barrier of the plasma membrane through lipid-lipid and lipid-protein interactions. The S. cerevisiae pathogen-related yeast proteins 1, 2, and 3 (Pry) belong to a large protein superfamily known as CAP/SCP/TAPS. Members of this superfamily have been implicated in a wide variety of processes, including immune defense in mammals and plants, pathogen virulence, sperm maturation and fertilization, venom toxicity, and prostate and brain cancer...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28710283/amorphous-protein-aggregates-stimulate-plasminogen-activation-leading-to-release-of-cytotoxic-fragments-that-are-clients-for-extracellular-chaperones
#19
Patrick Constantinescu, Rebecca A Brown, Amy R Wyatt, Marie Ranson, Mark R Wilson
The misfolding of proteins and their accumulation in extracellular tissue compartments as insoluble amyloid or amorphous protein aggregates is a hallmark feature of many debilitating protein deposition diseases such as Alzheimers disease, prion diseases and type II diabetes. The plasminogen activation system (PAS) is best known as an extracellular fibrinolytic system, but was previously reported to also be capable of degrading amyloid fibrils. Here we show that amorphous protein aggregates interact with tPA and plasminogen, via an exposed lysine dependent mechanism, to efficiently generate plasmin...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28710280/the-assembly-of-the-plant-urease-activation-complex-and-the-essential-role-of-the-urease-accessory-protein-g-ureg-in-delivery-of-nickel-to-urease
#20
Till Myrach, Anting Zhu, Claus-Peter Witte
Urease is a ubiquitous nickel metalloenzyme. In plants, its activation requires three urease accessory proteins (UAPs), UreD, UreF, and UreG. In bacteria, the UAPs interact with urease and facilitate activation, which involves the channeling of two nickel ions into the active site. So far this process has not been investigated in eukaryotes. Using affinity pull-downs of Strep-tagged UAPs from Arabidopsis and rice transiently expressed in planta, we demonstrate that a urease:UreD:UreF:UreG complex exists in plants and show its stepwise assembly...
July 14, 2017: Journal of Biological Chemistry
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