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https://www.readbyqxmd.com/read/29163217/different-principles-of-adp-ribose-mediated-activation-and-opposite-roles-of-the-nudt9-homology-domain-in-the-trpm2-orthologs-of-man-and-sea-anemone
#1
REVIEW
Frank Kühn, Cornelia Kühn, Andreas Lückhoff
A decisive element in the human cation channel TRPM2 is a region in its cytosolic C-terminus named NUDT9H because of its homology to the NUDT9 enzyme, a pyrophosphatase degrading ADP-ribose (ADPR). In hTRPM2, however, the NUDT9H domain has lost its enzymatic activity but serves as a binding domain for ADPR. As consequence of binding, gating of the channel is initiated. Since ADPR is produced after oxidative DNA damage, hTRPM2 mediates Ca(2+) influx in response to oxidative stress which may lead to cell death...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29155817/analysis-of-the-interactome-of-schistosoma-mansoni-histone-deacetylase-8
#2
Stéphanie Caby, Lucile Pagliazzo, Julien Lancelot, Jean-Michel Saliou, Nicolas Bertheaume, Raymond J Pierce, Emmanuel Roger
BACKGROUND: Histone deacetylase 8 from Schistosoma mansoni (SmHDAC8) is essential to parasite growth and development within the mammalian host and is under investigation as a target for the development of selective inhibitors as novel schistosomicidal drugs. Although some protein substrates and protein partners of human HDAC8 have been characterized, notably indicating a role in the function of the cohesin complex, nothing is known of the partners and biological function of SmHDAC8. METHODOLOGY/PRINCIPAL FINDINGS: We therefore employed two strategies to characterize the SmHDAC8 interactome...
November 20, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29155101/type-i-ifn-related-netosis-in-ataxia-telangiectasia-and-artemis-deficiency
#3
Ersin Gul, Esra Hazar Sayar, Bilgi Gungor, Fehime Kara Eroglu, Naz Surucu, Sevgi Keles, Sukru Nail Guner, Sıddıka Fındık, Esin Alpdündar, Ihsan Cihan Ayanoglu, Basak Kayaoglu, Busra Nur Geçkin, Hatice Asena Sanli, Tamer Kahraman, Cengiz Yakicier, Meltem Muftuoglu, Berna Oguz, Deniz Nazire Cagdas Ayvaz, Ihsan Gursel, Seza Ozen, Ismail Reisli, Mayda Gursel
BACKGROUND: Pathological inflammatory syndromes of unknown etiology are commonly observed in Ataxia telangiectasia (AT) and Artemis deficiency. Similar inflammatory manifestations also exist in STING-associated vasculopathy in infancy (SAVI) patients. OBJECTIVE: To test the hypothesis that the inflammation associated manifestations observed in AT and Artemis deficient patients stem from increased type I IFN signature leading to neutrophil mediated pathological damage...
November 15, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29150429/cgamp-a-tale-of-two-signals
#4
Teneema Kuriakose, Thirumala-Devi Kanneganti
In this issue of JEM, Swanson et al. (https://doi.org/10.1084/jem.20171749) report an unanticipated role for cGAMP in priming and activation of inflammasomes in addition to its well-characterized function as an endogenous second messenger inducing type I interferons in the cytosolic DNA-sensing pathway.
November 17, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29149408/function-of-translationally-controlled-tumor-protein-in-organ-growth-lessons-from-drosophila-studies
#5
Kwang-Wook Choi, Sung-Tae Hong, Thao Phuong Le
Regulation of cell growth and proliferation is crucial for development and function of organs in all animals. Genetic defects in growth control can lead to developmental disorders and cancers. Translationally controlled tumor protein (TCTP) is a family of evolutionarily conserved proteins implicated in cancer. Recent studies have revealed multiple roles of TCTP in diverse cellular events, but TCTP functions in vivo are poorly understood in vertebrate systems. We have used Drosophila melanogaster, the fruit fly, as a model organism for genetic dissection of Tctp function...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29146913/autophagy-acts-through-traf3-and-relb-to-regulate-gene-expression-via-antagonism-of-smad-proteins
#6
Alice C Newman, Alain J Kemp, Yvette Drabsch, Christian Behrends, Simon Wilkinson
Macroautophagy can regulate cell signalling and tumorigenesis via elusive molecular mechanisms. We establish a RAS mutant cancer cell model where the autophagy gene ATG5 is dispensable in A549 cells in vitro, yet promotes tumorigenesis in mice. ATG5 represses transcriptional activation by the TGFβ-SMAD gene regulatory pathway. However, autophagy does not terminate cytosolic signal transduction by TGFβ. Instead, we use proteomics to identify selective degradation of the signalling scaffold TRAF3. TRAF3 autophagy is driven by RAS and results in activation of the NF-κB family member RELB...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29141238/rationale-redesign-of-type-iii-secretion-systems-toward-the-development-of-non-pathogenic-e-coli-for-in-vivo-delivery-of-therapeutic-payloads
#7
REVIEW
Coral González-Prieto, Cammie F Lesser
Transkingdom secretion systems that bacteria use to inject proteins directly into the cytosol of mammalian host cells play an essential role in the virulence of many Gram-negative bacterial pathogens. Current efforts are underway to repurpose these machines as novel therapeutics; type III secretion systems as vectors for the delivery of proteins of therapeutic value including heterologous antigens for vaccine development and type IV secretion systems as vectors for DNA. While initial studies focused on the use of attenuated or replication incompetent pathogens, the recent development of non-pathogenic Escherichia coli that encode programmable type III secretion systems expands possibilities for the in vivo directed delivery of therapeutic payloads...
November 12, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29140245/bacterial-fumarase-and-l-malic-acid-are-evolutionary-ancient-components-of-the-dna-damage-response
#8
Esti Singer, Yardena Bh Silas, Sigal Ben-Yehuda, Ophry Pines
Fumarase is distributed between two compartments of the eukaryotic cell. The enzyme catalyses the reversible conversion of fumaric to L-malic acid in mitochondria as part of the tricarboxylic acid (TCA) cycle, and in the cytosol/nucleus as part of the DNA damage response (DDR). Here we show that fumarase of the model prokaryote Bacillus subtilis (Fum-bc) is induced upon DNA damage, co-localized with the bacterial DNA and is required for the DDR. Fum-bc can substitute for both eukaryotic functions in yeast. Furthermore, we found that the fumarase dependent intracellular signaling of the B...
November 15, 2017: ELife
https://www.readbyqxmd.com/read/29137983/transcriptional-regulation-of-acetoacetyl-coa-synthetase-by-sp1-in-neuroblastoma-cells
#9
Shinya Hasegawa, Masahiko Imai, Masahiro Yamasaki, Noriko Takahashi, Tetsuya Fukui
Acetoacetyl-CoA synthetase (AACS) is the enzyme responsible for cholesterol and fatty acid synthesis in the cytosol. We have previously shown that AACS has an important role in normal neuronal development and that knockdown of SREBP-2, which orchestrates cholesterol synthesis, resulted in the downregulation of AACS mRNA levels. In this study, we investigated the transcriptional mechanism of AACS in Neuro-2a, neuroblastoma cells. Luciferase assay showed that the minimal core promoter of the mouse AACS gene is located in a region with 110 bps upstream from the transcription start site...
November 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29133134/sensing-the-breaks-cytosolic-chromatin-in-senescence-and-cancer
#10
Raffaella Di Micco
Cellular senescence constitutes a stable growth arrest characterized by DNA damage response (DDR) activation and by the senescence-associated secretory phenotype (SASP). SASP, through its paracrine effects, stimulates the immune system for senescence eradication. Similarly, chemotherapy-treated cancers activate an interferon-mediated response to induce anti-tumor immunity. Recent studies now uncover a new role for the innate DNA sensing pathway in the recognition of cytosolic chromatin in senescence and cancer...
November 10, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29128691/type-i-interferon-mediated-autoinflammation-and-autoimmunity
#11
REVIEW
Stefanie Kretschmer, Min Ae Lee-Kirsch
The monogenic type I interferonopathies comprise a heterogenous group of disorders of the innate immune system associated with constitutive activation of antiviral type I interferon (IFN). Despite a remarkable phenotypic diversity, type I interferonopathies are commonly characterized by autoinflammation and varying degrees of autoimmunity or immunodeficiency. The elucidation of the underlying genetic causes has revealed novel cell-intrinsic mechanisms that protect the organism against inappropriate immune recognition of self nucleic acids by cytosolic sensors such as cGAS or MDA5 through metabolizing or processing of intracellular DNA or RNA...
November 9, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29124689/xeroderma-pigmentosa-group-a-xpa-nucleotide-excision-repair-and-regulation-by-atr-in-response-to-ultraviolet-irradiation
#12
Phillip R Musich, Zhengke Li, Yue Zou
The sensitivity of Xeroderma pigmentosa (XP) patients to sunlight has spurred the discovery and genetic and biochemical analysis of the eight XP gene products (XPA-XPG plus XPV) responsible for this disorder. These studies also have served to elucidate the nucleotide excision repair (NER) process, especially the critical role played by the XPA protein. More recent studies have shown that NER also involves numerous other proteins normally employed in DNA metabolism and cell cycle regulation. Central among these is ataxia telangiectasia and Rad3-related (ATR), a protein kinase involved in intracellular signaling in response to DNA damage, especially DNA damage-induced replicative stresses...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29121649/spatiotemporal-dynamics-of-hsv-genome-nuclear-entry-and-compaction-state-transitions-using-bioorthogonal-chemistry-and-super-resolution-microscopy
#13
Eiki Sekine, Nora Schmidt, David Gaboriau, Peter O'Hare
We investigated the spatiotemporal dynamics of HSV genome transport during the initiation of infection using viruses containing bioorthogonal traceable precursors incorporated into their genomes (HSVEdC). In vitro assays revealed a structural alteration in the capsid induced upon HSVEdC binding to solid supports that allowed coupling to external capture agents and demonstrated that the vast majority of individual virions contained bioorthogonally-tagged genomes. Using HSVEdC in vivo we reveal novel aspects of the kinetics, localisation, mechanistic entry requirements and morphological transitions of infecting genomes...
November 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29118920/combination-therapy-with-extracorporeal-shock-wave-and-melatonin-markedly-attenuated-neuropathic-pain-in-rat
#14
Kuan-Hung Chen, Chien-Hui Yang, Christopher Glenn Wallace, Chung-Ren Lin, Chia-Kai Liu, Tsung-Cheng Yin, Tien-Hung Huang, Yi-Ling Chen, Cheuk-Kwan Sun, Hon-Kan Yip
This study tested the hypothesis that combination therapy using extracorporeal shock wave (ECSW)-melatonin (Mel) was superior to either alone at ameliorating neuropathic pain (NP). NP was induced by chronic constriction injury (CCI) to the left sciatic nerve in rats. Animals were categorized into sham control (group 1), CCI only (group 2), CCI-ECSW (group 3), CCI-Mel (group 4) and CCI-ECSW-Mel (group 5). By days 2 and 8 after CCI, the mechanical paw withdrawal threshold (MPWT)/thermal paw withdrawal latency (TPWL) were highest in group 2, lowest in group 1, significantly lower in group 5 than in groups 3 and 4 (all p<0...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29114584/expression-purification-and-characterization-of-hepatitis-b-virus-x-protein-bh3-like-motif-linker-bcl-xl-fusion-protein-for-structural-studies
#15
Hideki Kusunoki, Toshiyuki Tanaka, Toshiyuki Kohno, Hirokazu Kimura, Kazuo Hosoda, Kaori Wakamatsu, Isao Hamaguchi
Hepatitis B virus X protein (HBx) is a multifunctional protein that interacts directly with many host proteins. For example, HBx interacts with anti-apoptotic proteins, Bcl-2 and Bcl-xL, through its BH3-like motif, which leads to elevated cytosolic calcium levels, efficient viral DNA replication and the induction of apoptosis. To facilitate sample preparation and perform detailed structural characterization of the complex between HBx and Bcl-xL, we designed and purified a recombinant HBx BH3-like motif-linker-Bcl-xL fusion protein produced in E...
March 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29113909/the-chaperone-dynein-ll1-mediates-cytoplasmic-transport-of-empty-and-mature-hepatitis-b-virus-capsids
#16
Quentin Osseman, Lara Gallucci, Shelly Au, Christian Cazenave, Elodie Berdance, Marie-Lise Blondot, Aurélia Cassany, Dominique Bégu, Jessica Ragues, Cindy Aknin, Irina Sominskaya, Andris Dishlers, Birgit Rabe, Fenja Anderson, Nelly Panté, Michael Kann
BACKGROUND & AIMS: Hepatitis B virus (HBV) has a DNA genome but replicates within nucleus by transcription of an RNA pregenome, which is converted to DNA in cytoplasmic capsids. Capsids in this compartment are correlated with inflammation and epitopes of the capsid protein core (Cp) are the main target for T cell-mediated immune response. We investigated the mechanism of cytoplasmic capsid transport, which is important for infection but also for cytosolic capsid removal. METHODS: We used virion-derived capsids with a mature rcDNA (matC), empty capsids (empC), and RNA containing capsids (rnaC) as control...
November 4, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/29113421/oxidative-stress-induced-diseases-and-tea-polyphenols
#17
REVIEW
Xiangbing Mao, Changsong Gu, Daiwen Chen, Bing Yu, Jun He
Reactive oxide species are the middle products of normal metabolism, and play a crucial role in cell signaling transduction. On the contrary, accumulation of excess reactive oxide species results in oxidative stress that often brings multifarious impairment to cells, including decrease of ATP level in cells, elevation of cytosolic Ca(2+), DNA damage, dysfunction of biological function in lipid bilayer and so on. These effects will finally lead to all kinds of diseases. Tea polyphenols are widely considered as a kind of excellent antioxidant agents...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29109780/metabolomic-profiling-of-extracellular-vesicles-and-alternative-normalization-methods-reveal-enriched-metabolites-and-strategies-to-study-prostate-cancer-related-changes
#18
Maija Puhka, Maarit Takatalo, Maria-Elisa Nordberg, Sami Valkonen, Jatin Nandania, Maria Aatonen, Marjo Yliperttula, Saara Laitinen, Vidya Velagapudi, Tuomas Mirtti, Olli Kallioniemi, Antti Rannikko, Pia R-M Siljander, Taija Maria Af Hällström
Body fluids are a rich source of extracellular vesicles (EVs), which carry cargo derived from the secreting cells. So far, biomarkers for pathological conditions have been mainly searched from their protein, (mi)RNA, DNA and lipid cargo. Here, we explored the small molecule metabolites from urinary and platelet EVs relative to their matched source samples. As a proof-of-concept study of intra-EV metabolites, we compared alternative normalization methods to profile urinary EVs from prostate cancer patients before and after prostatectomy and from healthy controls...
2017: Theranostics
https://www.readbyqxmd.com/read/29109257/ribonucleotides-incorporated-by-the-yeast-mitochondrial-dna-polymerase-are-not-repaired
#19
Paulina H Wanrooij, Martin K M Engqvist, Josefin M E Forslund, Clara Navarrete, Anna Karin Nilsson, Juhan Sedman, Sjoerd Wanrooij, Anders R Clausen, Andrei Chabes
Incorporation of ribonucleotides into DNA during genome replication is a significant source of genomic instability. The frequency of ribonucleotides in DNA is determined by deoxyribonucleoside triphosphate/ribonucleoside triphosphate (dNTP/rNTP) ratios, by the ability of DNA polymerases to discriminate against ribonucleotides, and by the capacity of repair mechanisms to remove incorporated ribonucleotides. To simultaneously compare how the nuclear and mitochondrial genomes incorporate and remove ribonucleotides, we challenged these processes by changing the balance of cellular dNTPs...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29107116/mitophagy-and-the-release-of-inflammatory-cytokines
#20
REVIEW
James Harris, Nadia Deen, Shahrzad Zamani, Md Abul Hasnat
Mitophagy is a selective form of autophagy in which damaged or dysfunctional mitochondria are specifically targeted by autophagosomes for lysosomal degradation. Studies have demonstrated that loss of autophagy/mitophagy can lead to a build-up of cytosolic reactive oxygen species and mitochondrial DNA, which can, in turn, activate immune signalling pathways that ultimately lead to the releases of inflammatory cytokines, including IL-1α, IL-1β, IL-18 and macrophage migration inhibitory factor (MIF). Moreover, release of these cytokines can subsequently promote the release of others, including IL-23 and IL-17...
October 26, 2017: Mitochondrion
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