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https://www.readbyqxmd.com/read/27914200/assembling-the-tat-protein-translocase
#1
Felicity Alcock, Phillip J Stansfeld, Hajra Basit, Johann Habersetzer, Matthew Ab Baker, Tracy Palmer, Mark I Wallace, Ben C Berks
The twin-arginine protein translocation system (Tat) transports folded proteins across the bacterial cytoplasmic membrane and the thylakoid membranes of plant chloroplasts. The Tat transporter is assembled from multiple copies of the membrane proteins TatA, TatB, and TatC. We combine sequence co-evolution analysis, molecular simulations, and experimentation to define the interactions between the Tat proteins of Escherichia coli at molecular-level resolution. In the TatBC receptor complex the transmembrane helix of each TatB molecule is sandwiched between two TatC molecules, with one of the inter-subunit interfaces incorporating a functionally important cluster of interacting polar residues...
December 3, 2016: ELife
https://www.readbyqxmd.com/read/27913954/the-anti-inflammatory-activities-of-two-major-withanolides-from-physalis-minima-via-acting-on-nf-%C3%AE%C2%BAb-stat3-and-ho-1-in-lps-stimulated-raw264-7-cells
#2
Rui-Jun Li, Cai-Yun Gao, Chao Guo, Miao-Miao Zhou, Jun Luo, Ling-Yi Kong
Physalis minima has been traditionally used as a folk herbal medicine in China for the treatment of many inflammatory diseases. However, little is known about its anti-inflammatory constituents and associated molecular mechanisms. In our study, withaphysalin A (WA) and 2, 3-dihydro-withaphysalin C (WC), two major withanolide-type compounds, were obtained from the anti-inflammatory fraction of P. minima. Both WA and WC significantly inhibited the production of nitrite oxide (NO), prostaglandin E2 (PGE2), and several pro-inflammatory cytokines, such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-activated RAW264...
December 2, 2016: Inflammation
https://www.readbyqxmd.com/read/27913733/identification-of-2-methylthio-cyclic-n6-threonylcarbamoyladenosine-ms2ct6a-as-a-novel-rna-modification-at-position-37-of-trnas
#3
Byeong-Il Kang, Kenjyo Miyauchi, Michal Matuszewski, Gabriel Silveira D'Almeida, Mary Anne T Rubio, Juan D Alfonzo, Kazuki Inoue, Yuriko Sakaguchi, Takeo Suzuki, Elzbieta Sochacka, Tsutomu Suzuki
Transfer RNA modifications play pivotal roles in protein synthesis. N(6)-threonylcarbamoyladenosine (t(6)A) and its derivatives are modifications found at position 37, 3'-adjacent to the anticodon, in tRNAs responsible for ANN codons. These modifications are universally conserved in all domains of life. t(6)A and its derivatives have pleiotropic functions in protein synthesis including aminoacylation, decoding and translocation. We previously discovered a cyclic form of t(6)A (ct(6)A) as a chemically labile derivative of t(6)A in tRNAs from bacteria, fungi, plants and protists...
December 2, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27913212/vcp-cooperates-with-ubxd1-to-degrade-mitochondrial-outer-membrane-protein-mcl1-in-model-of-huntington-s-disease
#4
Xing Guo, Xin Qi
Proteasome-dependent turnover of mitochondrial outer membrane (OMM)-associated proteins is one of the mechanisms for maintaining proper mitochondrial quality and function. However, the underlying pathways and their implications in human disease are poorly understood. Huntington's disease (HD) is a fatal, inherited neurodegenerative disorder caused by expanded CAG repeats in the N terminal of the huntingtin gene (mutant Huntingtin, mtHtt). In this study, we show an extensive degradation of the OMM protein MCL1 (Myeloid cell leukemia sequence 1) in both HD mouse striatal cells and HD patient fibroblasts...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27913144/effect-of-o-glcnacylation-on-hnrnp-a1-translocation-and-interaction-with-transportin1
#5
Shira Roth, Isam Khalaila
The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a major pre-mRNA binding protein involved in transcription and translation. Although predominantly nuclear, hnRNP A1 shuttles rapidly between the nucleus and the cytosol, delivering its anchored pre-mRNA for further processing. Translocation is important for hnRNP A1 to accomplish its transcriptional and translational roles. Transportin1 (Trn1), a translocation protein, facilitates the translocation of hnRNP A1 back to the nucleus. Moreover, phosphorylation of serine residues at hnRNP A1 C-terminal domain affects its translocation...
November 29, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27912883/miltirone-protects-human-ea-hy926-endothelial-cells-from-oxidized-low-density-lipoprotein-derived-oxidative-stress-via-a-heme-oxygenase-1-and-mapk-nrf2-dependent-pathway
#6
Liu Zhang, Hui Zhang, Xueyan Li, Bingjie Jia, Yuyu Yang, Ping Zhou, Ping Li, Jun Chen
BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) is an underlying cause of endothelial dysfunction, which is an early event in the pathogenesis of atherosclerosis. In our previous study, we established an ARE-driven luciferase reporter system and screened out several potential Nrf2 activators from Salvia miltiorrhiza Bunge. PURPOSE: Since miltirone showed the most potent ARE-driven luciferase activity, the aim of this study was to test the protective role of miltirone against oxidative stress in endothelial cell and to investigate the underlying mechanistic signaling pathways...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27912767/lipocalin2-suppresses-metastasis-of-colorectal-cancer-by-attenuating-nf-%C3%AE%C2%BAb-dependent-activation-of-snail-and-epithelial-mesenchymal-transition
#7
Meibao Feng, Jieqiong Feng, Wuzhen Chen, Wubin Wang, Xuesong Wu, Jing Zhang, Fangying Xu, Maode Lai
BACKGROUND: Lipocalin2 (LCN2) is a secretory protein that is aberrantly expressed in several types of cancer and has been involved in metastatic progression. However, neither mechanisms nor the role that LCN2 plays in the metastasis of colorectal cancer are clear. METHODS: LCN2 expression in colorectal cancer was detected by immunohistochemistry in 400 tissue specimens and Kaplan-Meier survival analysis was performed. In vitro, real-time PCR, western blot, colony formation assay, immunofluorescence assay, wound healing assay, migration and invasion experiment were performed to investigate the effects of LCN2 in epithelial mesenchymal transition (EMT), migration and invasion, respectively...
December 3, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27912750/fermented-barley-and-soybean-bs-mixture-enhances-intestinal-barrier-function-in-dextran-sulfate-sodium-dss-induced-colitis-mouse-model
#8
Jong Kyu Woo, Seungho Choi, Ju-Hee Kang, Dae Eung Kim, Byung-Serk Hurh, Jong-Eun Jeon, Sun Yeou Kim, Seung Hyun Oh
BACKGROUND: Inflammatory bowel disease (IBD) is characterized by chronic or relapsing immune system activation and inflammation within the gastrointestinal tract. The lack of safety and efficacy of standard therapies, the use of food supplements for managing IBD is increasing, and many studies have reported that various food supplements provide many beneficial effects for the IBD. METHODS: This study aimed to evaluate the anti-colitis effects of dietary supplementation with a fermented barley and soybean mixture (BS) on intestinal inflammation using a murine model of IBD...
December 3, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27911872/p120-regulates-beta-catenin-nuclear-translocation-through-e-cadherin-endocytosis-in-ventilator-induced-lung-injury
#9
Changping Gu, Chenyang Dai, Yongtao Sun, Mengjie Liu, Yuelan Wang, Xinyi Wu
Mechanical stretch induces epithelial barrier dysfunction by altering the location and degradation of cellular junction proteins. p120-catenin (p120) is a cell-cell junction protein known to protect against ventilator-induced lung injury (VILI) that results from improper ventilation of patients. In this study, we sought to determine the role of p120 in VILI and its relationship with the cellular response to mechanical stretch. Mouse lung epithelial cells (MLE-12) transfected with p120 siRNA, p120 cDNA, or E-cadherin siRNA were subjected to 20% cyclic stretch for 2 or 4 hours...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911384/analysis-of-scap-n-glycosylation-and-trafficking-in-human-cells
#10
Chunming Cheng, Jeffrey Yunhua Guo, Feng Geng, Xiaoning Wu, Xiang Cheng, Qiyue Li, Deliang Guo
Elevated lipogenesis is a common characteristic of cancer and metabolic diseases. Sterol regulatory element-binding proteins (SREBPs), a family of membrane-bound transcription factors controlling the expression of genes important for the synthesis of cholesterol, fatty acids and phospholipids, are frequently upregulated in these diseases. In the process of SREBP nuclear translocation, SREBP-cleavage activating protein (SCAP) plays a central role in the trafficking of SREBP from the endoplasmic reticulum (ER) to the Golgi and in subsequent proteolysis activation...
November 8, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27910767/immunostimulatory-effects-of-melphalan-and-usefulness-in-adoptive-cell-therapy-with-antitumor-cd4-t-cells
#11
Michal Kuczma, Zhi-Chun Ding, Gang Zhou
The alkylating agent melphalan is used in the treatment of hematological malignancies, especially multiple myeloma. In the past, the usefulness of melphalan has been solely attributed to its cytotoxicity on fastgrowing cancerous cells. Although the immunomodulatory effects of melphalan were suggested many years ago, only recently has this aspect of melphalan's activity begun to be elucidated at the molecular level. Emerging evidence indicates that melphalan can foster an immunogenic microenvironment by inducing immunogenic cell death (ICD) as characterized by membrane translocation of endoplasmic reticulum protein calreticulin (CRT) and by release of chromatin-binding protein high-mobility group box 1 (HMGB1)...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27910150/randomised-clinical-trial-exploratory-phase-2-study-of-ono-2952-in-diarrhoea-predominant-irritable-bowel-syndrome
#12
W E Whitehead, K Duffy, J Sharpe, T Nabata, M Bruce
BACKGROUND: ONO-2952 is a novel and selective inhibitor of translocator protein 18 kDa that reduces stress-induced defecation and visceral hyperalgesia in rat models. AIM: To evaluate the efficacy and safety of ONO-2952 in females with irritable bowel syndrome with diarrhoea in an exploratory proof-of-concept study. METHODS: A randomised, double-blind, placebo-controlled study was conducted at 49 US centres. Two hundred subjects with irritable bowel syndrome with diarrhoea (Rome III criteria) were randomised to ONO-2952 20 mg, or 60 mg, or placebo...
January 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27909300/cyanobacterial-photoprotection-by-the-orange-carotenoid-protein
#13
REVIEW
Diana Kirilovsky, Cheryl A Kerfeld
In photosynthetic organisms, the production of dangerous oxygen species is stimulated under high irradiance. To cope with this stress, these organisms have evolved photoprotective mechanisms. One type of mechanism functions to decrease the energy arriving at the photochemical centres by increasing thermal dissipation at the level of antennae. In cyanobacteria, the trigger for this mechanism is the photoactivation of a soluble carotenoid protein, the orange carotenoid protein (OCP), which is a structurally and functionally modular protein...
December 2, 2016: Nature Plants
https://www.readbyqxmd.com/read/27909247/integration-of-transmembrane-domains-is-regulated-by-their-downstream-sequences
#14
Tina Junne, Martin Spiess
The Sec61 translocon catalyzes translocation of proteins into the endoplasmic reticulum and the lateral integration of transmembrane segments into the lipid bilayer. Integration is mediated by the hydrophobicity of a polypeptide segment consistent with thermodynamic equilibration between the translocon and the lipid membrane. Integration efficiency of a generic series of increasingly hydrophobic sequences (H-segments) was found to diverge significantly in different reporter constructs as a function of the ∼100 residues carboxyterminal of the H-segments...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27908834/gamma-secretase-inhibitor-impairs-epithelial-to-mesenchymal-transition-induced-by-tgf-%C3%AE-in-ovarian-tumor-cell-lines
#15
M C Pazos, D Abramovich, A Bechis, P Accialini, F Parborell, M Tesone, G Irusta
Ovarian cancer is characterized by being highly metastatic, a feature that represents the main cause of failure of the treatment. This study investigated the effects of γ-secretase inhibition on the TGF-β-induced epithelial-mesenchymal transition (EMT) process in ovarian cancer cell lines. SKOV3 cells incubated in the presence of TGF-β showed morphological and biochemical changes related to EMT, which were blocked by co-stimulation with TGF-β and the γ-secretase inhibitor DAPT. In SKOV3 and IGROV1 cells, the co-stimulation blocked the cadherin switch and the increase in the transcription factors Snail, Slug, Twist and Zeb1 induced by TGF-β...
November 28, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27907195/novel-aryl-hydrocarbon-receptor-agonist-suppresses-migration-and-invasion-of-breast-cancer-cells
#16
Hamza Hanieh, Omar Mohafez, Villianur Ibrahim Hairul-Islam, Abdullah Alzahrani, Mohammad Bani Ismail, Krishnaraj Thirugnanasambantham
BACKGROUND: Despite the remarkable progress to fight against breast cancer, metastasis remains the dominant cause of treatment failure and recurrence. Therefore, control of invasiveness potential of breast cancer cells is crucial. Accumulating evidences suggest Aryl hydrocarbon receptor (Ahr), a helix-loop-helix transcription factor, as a promising target to control migration and invasion in breast cancer cells. Thus, an Ahr-based exploration was performed to identify a new Ahr agonist with inhibitory potentials on cancer cell motility...
2016: PloS One
https://www.readbyqxmd.com/read/27907166/vaccinia-virus-protein-c6-inhibits-type-i-ifn-signalling-in-the-nucleus-and-binds-to-the-transactivation-domain-of-stat2
#17
Jennifer H Stuart, Rebecca P Sumner, Yongxu Lu, Joseph S Snowden, Geoffrey L Smith
The type I interferon (IFN) response is a crucial innate immune signalling pathway required for defense against viral infection. Accordingly, the great majority of mammalian viruses possess means to inhibit this important host immune response. Here we show that vaccinia virus (VACV) strain Western Reserve protein C6, is a dual function protein that inhibits the cellular response to type I IFNs in addition to its published function as an inhibitor of IRF-3 activation, thereby restricting type I IFN production from infected cells...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27907096/global-deletion-of-tspo-does-not-affect-the-viability-and-gene-expression-profile
#18
Huaishan Wang, Kangle Zhai, Yingchao Xue, Jia Yang, Qi Yang, Yi Fu, Yu Hu, Fang Liu, Weiqing Wang, Lianxian Cui, Hui Chen, Jianmin Zhang, Wei He
Translocator Protein (18kDa, TSPO) is a mitochondrial outer membrane transmembrane protein. Its expression is elevated during inflammation and injury. However, the function of TSPO in vivo is still controversial. Here, we constructed a TSPO global knockout (KO) mouse with a Cre-LoxP system that abolished TSPO protein expression in all tissues and showed normal phenotypes in the physiological condition. The birth rates of TSPO heterozygote (Het) x Het or KO x KO breeding were consistent with Mendel's Law, suggesting a normal viability of TSPO KO mice at birth...
2016: PloS One
https://www.readbyqxmd.com/read/27907005/intraluminal-flagellin-differentially-contributes-to-gut-dysbiosis-and-systemic-inflammation-following-burn-injury
#19
Logan Grimes, Allie Doyle, Aaron L Miller, Richard B Pyles, Gabor Olah, Csaba Szabo, Sarah Hoskins, Tonyia Eaves-Pyles
Burn injury is associated with a loss of gut barrier function, resulting in systemic dissemination of gut-derived bacteria and their products. The bacterial protein and TLR5 agonist, flagellin, induces non-specific innate immune responses. Because we detected flagellin in the serum of burn patients, we investigated whether gut-derived flagellin was a primary or secondary contributor to intestinal dysfunction and systemic inflammation following burn injury. The apical surface of polarized human intestinal epithelial cells (IECs), Caco-2BBe, were exposed to 50 or 500 ng of purified flagellin and 1 x 105 of an intestinal E...
2016: PloS One
https://www.readbyqxmd.com/read/27906189/distinct-outcomes-of-crl-nedd8-pathway-inhibition-reveal-cancer-cell-plasticity
#20
Anastasia V Rulina, Frédérique Mittler, Patricia Obeid, Sophie Gerbaud, Laurent Guyon, Eric Sulpice, Frédérique Kermarrec, Nicole Assard, Monika E Dolega, Xavier Gidrol, Maxim Y Balakirev
Inhibition of protein degradation by blocking Cullin-RING E3 ligases (CRLs) is a new approach in cancer therapy though of unknown risk because CRL inhibition may stabilize both oncoproteins and tumor suppressors. Probing CRLs in prostate cancer cells revealed a remarkable plasticity of cells with TMPRSS2-ERG translocation. CRL suppression by chemical inhibition or knockdown of RING component RBX1 led to reversible G0/G1 cell cycle arrest that prevented cell apoptosis. Conversely, complete blocking of CRLs at a higher inhibitor dose-induced cytotoxicity that was amplified by knockdown of CRL regulator Cand1...
December 1, 2016: Cell Death & Disease
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