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Journal of Biological Chemistry

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https://www.readbyqxmd.com/read/28724635/heterodimers-of-the-transcriptional-factors-nfatc3-and-fosb-mediate-tissue-factor-expression-for-15-s-hydroxyeicosatetraenoic-acid-induced-monocyte-trafficking
#1
Sivareddy Kotla, Nikhlesh K Singh, Daniel Kirchhofer, Gadiparthi N Rao
Tissue factor (TF) is expressed in vascular and nonvascular tissues and functions in several pathways, including embryonic development, inflammation, and cell migration. Many risk factors for atherosclerosis, including hypertension, diabetes, obesity, and smoking, increase TF expression. To better understand the TF-related mechanisms in atherosclerosis, here we investigated the role of 12/15-lipoxygenase (12/15-LOX) in TF expression. 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), the major product of human 15-LOXs 1 and 2, induced TF expression and activity in a time-dependent manner in the human monocytic cell line THP1...
July 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28724634/adaptor-protein-p62-promotes-skin-tumor-growth-and-metastasis-and-is-induced-by-uva-radiation
#2
Ashley Sample, Baozhong Zhao, Lei Qiang, Yu-Ying He
Skin cancer is the most common cancer and exposure to ultraviolet (UV) radiation, namely UVA and UVB is the major risk factor for skin cancer development. UVA is significantly less effective in causing direct DNA damage than UVB, but UVA has been shown to increase skin cancer risk. The mechanism by which UVA contributes to skin cancer remains unclear. Here, using RNA-Seq, we show that UVA induces autophagy and lysosomal gene expression, including the autophagy receptor and substrate p62. We found that UVA activates the transcription factor EB (TFEB), a known regulator of autophagy and lysosomal gene expression, which, in turn, induces p62 transcription...
July 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28724633/conformationally-organized-lysine-isosteres-in-streptococcus-pyogenes-m-protein-mediate-direct-high-affinity-binding-to-human-plasminogen
#3
Yue Yuan, Jaroslav Zajicek, Cunjia Qiu, Vishwanatha Chandrahas, Shaun W Lee, Victoria A Ploplis, Francis J Castellino
The binding of human plasminogen (hPg) to the surface of the human pathogen Streptococcus pyogenes (GAS) and subsequent hPg activation to the protease plasmin generate a proteolytic surface that GAS employs to circumvent host innate immunity. Direct high-affinity binding of hPg/plasmin to pattern D GAS is fully recapitulated by the hPg kringle 2 domain (K2hPg) and a short internal peptide region (a1a2) of a specific subtype of bacterial surface M protein, present in all GAS pattern D strains. To better understand the nature of this binding, critical to the virulence of many GAS skin-tropic strains, we used high-resolution NMR to define the interaction of recombinant K2hPg with recombinant a1a2 (VKK38) of the M protein from GAS isolate NS455...
July 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28724632/hydrogen-peroxide-produced-by-superoxide-dismutase-sod-2-is-required-for-sperm-activation-in-caenorhabditis-elegans
#4
Taro Sakamoto, Hirotaka Imai
Superoxide dismutase (SOD) is a ubiquitous antioxidant enzyme that catalytically converts the superoxide radical to hydrogen peroxide (H2O2). In mammals, high SOD activity can be detected in sperm and seminal plasma, and a correlation between loss of SOD activity and male infertility has been observed; however, the underlying mechanisms remain to be clarified. Here, we report that the deletion of two major SOD genes in Caenorhabditis elegans, sod-1 and sod-2, cause sperm activation defects, thereby leading to a significant reduction in brood size...
July 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28724631/the-axl-kinase-domain-in-complex-with-a-macrocyclic-inhibitor-offers-first-structural-insights-into-an-active-tam-receptor-kinase
#5
Ketan S Gajiwala, Neil Grodsky, Ben Bolaños, Junli Feng, RoseAnn Ferre, Sergei Timofeevski, Meirong Xu, Brion W Murray, Ted W Johnson, Al Stewart
The receptor tyrosine kinase (RTK) family consisting of Tyro3, Axl and Mer (TAM) is one of the most recently identified RTK families. TAM receptors are upregulated postnatally and maintained at high levels in adults. They all play an important role in immunity, but Axl has also been implicated in cancer and therefore is a target in the discovery and development of novel therapeutics. However, of the three members of the TAM family, the Axl kinase domain is the only one that has so far eluded structure determination...
July 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28724630/altered-met-receptor-phosphorylation-and-lrp1-mediated-uptake-in-cells-lacking-carbohydrate-dependent-lysosomal-targeting
#6
Megan Aarnio-Peterson, Peng Zhao, Seok-Ho Yu, Courtney Christian, Heather Flanagan-Steet, Lance Wells, Richard Steet
Acid hydrolases utilize a carbohydrate-dependent mechanism for lysosomal targeting. These hydrolases acquire a mannose 6-phosphate tag by the action of the GlcNAc-1-phosphotransferase enzyme, allowing them to bind receptors and traffic to endosomes. Loss of GlcNAc-1-phosphotransferase results in hydrolase hypersecretion and profound lysosomal storage. Little, however, is known about how these cellular phenotypes affect the trafficking, activity and localization of surface glycoproteins. To address this question, we profiled the abundance of surface glycoproteins in WT and CRISPR-mediated GNPTAB-/- HeLa cells and identified changes in numerous glycoproteins including the uptake receptor LRP1 and multiple receptor tyrosine kinases...
July 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28724629/abrogation-of-heat-shock-factor-1-hsf1-phosphorylation-deregulates-its-activity-and-lowers-activation-threshold-leading-to-obesity-in-mice
#7
Xiongjie Jin, Aijun Qiao, Demetrius Moskophidis, Nahid F Mivechi
Heat shock factor 1 (Hsf1) is transcriptionally activated following exposure of mammalian cells to environmental insults and pathological conditions. The function of Hsf1 as a protector of cells and organisms towards a range of stress stimuli has been well-documented. However, how different Hsf1 post-transcriptional modifications affect its function in vivo is not understood. Hsf1 transcriptional activity is in part regulated by phosphorylation. Hsf1 phosphorylation of amino acid residues at S303 and S307 has been shown to repress Hsf1 transcriptional activity under normal physiological growth conditions...
July 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28726644/arabidopsis-calmodulin-like-protein-cml36-is-a-calcium-ca-2-sensor-that-interacts-with-the-plasma-membrane-ca-2-atpase-isoform-aca8-and-stimulates-its-activity
#8
Alessandra Astegno, Maria Cristina Bonza, Rosario Vallone, Valentina La Verde, Mariapina D'Onofrio, Laura Luoni, Barbara Molesini, Paola Dominici
Calmodulin-like (CML) proteins are major EF hand-containing, calcium (Ca(2+))-binding proteins with crucial roles in plant development and in coordinating plant stress tolerance. Given their abundance in plants, the properties of Ca(2+) sensors and identification of novel target proteins of CMLs deserve special attention. To this end, we recombinantly produced and biochemically characterized CML36 from Arabidopsis thaliana We analyzed Ca(2+) and Mg(2+) binding to the individual EF hands, observed metal-induced conformational changes, and identified a physiologically relevant target...
July 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28726643/reconstructed-ancestral-enzymes-reveal-that-negative-selection-drove-the-evolution-of-substrate-specificity-in-adp-dependent-kinases
#9
Víctor Castro-Fernandez, Alejandra Herrera-Morande, Ricardo Zamora, Felipe Merino, Felipe Gonzalez-Ordenes, Felipe Padilla-Salinas, Humberto M Pereira, Jose Brandão-Neto, Richard C Garratt, Victoria Guixe
One central goal in molecular evolution is to pinpoint the mechanisms and evolutionary forces that cause an enzyme to change its substrate specificity; however, these processes remain largely unexplored. Using the glycolytic ADP-dependent kinases of archaea, including the orders Thermococcales, Methanosarcinales, and Methanococcales, as a model and employing an approach involving paleoenzymology, evolutionary statistics, and protein structural analysis, we could track changes in substrate specificity during ADP-dependent kinase evolution along with the structural determinants of these changes...
July 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28726642/coordinated-transcriptional-control-of-adipocyte-triglyceride-lipase-atgl-by-transcription-factors-sp1-and-ppar%C3%AE-during-adipocyte-differentiation
#10
Debasish Roy, Kenneth T Farabaugh, Jing Wu, Alyssa Charrier, Cynthia Smas, Maria Hatzoglou, Kavitha Thirumurugan, David A Buchner
The breakdown of stored fat deposits into its components is a highly regulated process that maintains plasma levels of free fatty acids to supply energy to cells. Insulin-mediated transcription of Atgl, the enzyme that mediates the rate-limiting step in lipolysis, is a key point of this regulation. In conditions such as obesity or insulin resistance, Atgl transcription is often misregulated, which can contribute to overall disease progression. The mechanisms by which Atgl is induced during adipogenesis are not fully understood...
July 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28726641/a-plant-fungal-type-phosphoenolpyruvate-carboxykinase-located-in-the-parasite-mitochondrion-ensures-glucose-independent-survival-of-toxoplasma-gondii
#11
Richard Nitzsche, Özlem Günay-Esiyok, Maximilian Tischer, Vyacheslav Zagoriy, Nishith Gupta
Toxoplasma gondii is considered as one of the most successful intracellular pathogens, because it can reproduce in varied nutritional milieus, encountered in diverse host-cell types of essentially any warm-blooded organism. Our earlier work has demonstrated that the acute (tachyzoite) stage of T. gondii depends on cooperativity of glucose and glutamine catabolism to meet biosynthetic demands. Either of these two nutrients can sustain the parasite survival; however, what determines the metabolic plasticity has not been resolved yet...
July 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28726640/c1q-tnf-related-protein-6-ctrp6-links-obesity-to-adipose-tissue-inflammation-and-insulin-resistance
#12
Xia Lei, Marcus M Seldin, Hannah C Little, Nicholas Choy, Thomas Klonisch, G William Wong
Obesity is associated with chronic low-grade inflammation, and metabolic regulators linking obesity to inflammation have therefore received much attention. Secreted C1q/TNF-related proteins (CTRPs) are one such group of regulators that regulate glucose and fat metabolism in peripheral tissues and modulate inflammation in adipose tissue. We have previously shown that expression of CTRP6 is up-regulated in leptin-deficient mice and, conversely, down-regulated by the anti-diabetic drug, rosiglitazone. Here, we provide evidence for a novel role of CTRP6 in modulating both inflammation and insulin sensitivity...
July 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28726639/mitochondrial-calcium-uniporter-in-drosophila-transfers-calcium-between-the-endoplasmic-reticulum-and-mitochondria-in-oxidative-stress-induced-cell-death
#13
Sekyu Choi, Xianglan Quan, Sunhoe Bang, Heesuk Yoo, Jiyoung Kim, Jiwon Park, Kyu-Sang Park, Jongkyeong Chung
Mitochondrial calcium plays critical roles in diverse cellular processes ranging from energy metabolism to cell death. Previous studies have demonstrated that mitochondrial calcium uptake is mainly mediated by the mitochondrial calcium uniporter (MCU) complex. However, the roles of the MCU complex in calcium transport, signaling, and dysregulation by oxidative stress still remain unclear. Here, we confirmed that Drosophila MCU contains evolutionarily conserved structures and requires essential MCU regulator (EMRE) for its calcium channel activities...
July 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28726638/understanding-inhibitor-resistance-in-mps1-kinase-through-novel-biophysical-assays-and-structures
#14
Yoshitaka Hiruma, Andre Koch, Nazila Hazraty, Foteini Tsakou, Rene H Medema, Robbie P Joosten, Anastassis Perrakis
Monopolar spindle 1 (Mps1/TTK) is a protein kinase essential in mitotic checkpoint signalling, preventing anaphase until all chromosomes are properly attached to spindle microtubules. Mps1 has emerged as a potential target for cancer therapy, and a variety of compounds have been developed to inhibit its kinase activity. Mutations in the catalytic domain of Mps1 that give rise to inhibitor resistance, but retain catalytic activity and do not display cross-resistance to other Mps1 inhibitors, have been described...
July 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28726637/microrna-101-attenuates-pulmonary-fibrosis-by-inhibiting-fibroblast-proliferation-and-activation
#15
Chaoqun Huang, Xiao Xiao, Ye Yang, Amarjit Mishra, Yurong Liang, Xiangming Zeng, Xiaoyun Yang, Dao Xu, Michael R Blackburn, Craig A Henke, Lin Liu
Aberrant proliferation and activation of lung fibroblasts contribute to the initiation and progression of idiopathic pulmonary fibrosis (IPF). However, the mechanisms responsible for the proliferation and activation of fibroblasts are not fully understood. The objective of the current study was to investigate the role of miR-101 in the proliferation and activation of lung fibroblasts. miR-101 expression was determined in lung tissues from patients with IPF and mice with bleomycin-induced pulmonary fibrosis...
July 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28726636/live-cell-visualization-of-gasdermin-d-driven-pyroptotic-cell-death
#16
Joseph K Rathkey, Bryan L Benson, Steven M Chirieleison, Jie Yang, Tsan S Xiao, George R Dubyak, Alex Y Huang, Derek W Abbott
Pyroptosis is a form of cell death important in defenses against pathogens, but which can also result in a potent and sometimes pathological inflammatory response. During pyroptosis, gasdermin D (GSDMD), the pore-forming effector protein, is cleaved, forms oligomers, and inserts into the membranes of the cell, resulting in rapid cell death. However, the potent cell death induction caused by GSDMD has complicated our ability to understand the biology of this protein. Studies aimed at visualizing GSDMD have relied on expression of GSDMD fragments in epithelial cell lines that naturally lack GSDMD expression and also lack the proteases necessary to cleave GSDMD...
July 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28718450/dynamics-and-energetics-of-the-mammalian-phosphatidylinositol-transfer-protein-phospholipid-exchange-cycle
#17
Aby Grabon, Adam Orlowski, Ashutosh Tripathi, Joni Vuorio, Matti Javanainen, Tomasz Róg, Max Lönnfors, Mark I McDermott, Garland Siebert, Pentti Somerharju, Ilpo Vattulainen, Vytas A Bankaitis
Phosphatidylinositol-transfer proteins (PITPs) regulate phosphoinositide signaling in eukaryotic cells. The defining feature of PITPs is their ability to exchange phosphatidylinositol (PtdIns) molecules between membranes, and this property is central to PITP-mediated regulation of lipid signaling. Yet, the details of the PITP-mediated lipid exchange cycle remain entirely obscure. Here, all-atom molecular dynamics (MD) simulations of the mammalian StART-like PtdIns/ phosphatidylcholine (PtdCho) transfer protein PITPα, both on membrane bilayers and in solvated systems, informed downstream biochemical analyses that tested key aspects of the hypotheses generated by the MD simulations...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28717011/dysregulation-of-bcl-2-family-proteins-by-leukaemia-fusion-genes
#18
Lauren M Brown, Diane T Hanna, Seong L Khaw, Paul G Ekert
The genomic lesions that characterise acute lymphoblastic leukaemia in childhood include recurrent translocations that result in the expression of fusion proteins. These translocations typically involve the rearrangement of genes encoding tyrosine kinases, including receptor tyrosine kinase, cytokine receptors and transcription factors. These confer phenotypic changes that are the hallmarks of malignant transformation, including unrestricted proliferation and a relative resistance to apoptosis. In this review, we explore the molecular mechanisms that link these fusions to the control of cell death...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28717010/phosphorylation-of-the-kainate-receptor-kar-auxiliary-subunit-neto2-at-serine-409-regulates-synaptic-targeting-of-the-kar-subunit-gluk1
#19
Richa Madan Lomash, Nengyin Sheng, Yan Li, Roger A Nicoll, Katherine W Roche
Synaptic strength at excitatory synapses is determined by the presence of glutamate receptors (i.e. AMPA, NMDA and kainate receptors) at the synapse. Synaptic strength is modulated by multiple factors including assembly of different receptor subunits, interaction with auxiliary subunits and post translational modifications of either the receptors or their auxiliary subunits. Using mass spectrometry, we find that the intracellular region of neuropilin and tolloid-like proteins (Neto)1 and Neto2, the auxiliary subunits of KARs are phosphorylated by multiple kinases in vitro...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28717009/acetylation-on-histone-h3-lysine-9-mediates-a-switch-from-transcription-initiation-to-elongation
#20
Leah A Gates, Jiejun Shi, Aarti D Rohira, Qin Feng, Bokai Zhu, Mark T Bedford, Cari A Sagum, Sung Yun Jung, Jun Qin, Ming-Jer Tsai, Sophia Y Tsai, Wei Li, Charles E Foulds, Bert W O'Malley
The transition from transcription initiation to elongation is a key regulatory step in gene expression, which requires RNA polymerase II (Pol II) to escape promoter proximal pausing on chromatin. While elongation factors promote pause release leading to transcription elongation, the role of epigenetic modifications during this critical transition step is poorly understood. Two histone marks on histone H3, lysine 4 trimethylation (H3K4me3) and lysine 9 acetylation (H3K9ac), co-localize on active gene promoters and are associated with active transcription...
July 17, 2017: Journal of Biological Chemistry
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