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cytosolic DNA

Hackwon Do, Nishanth Makthal, Arica R VanderWal, Mandy Rettel, Mikhail M Savitski, Nikolai Peschek, Kai Papenfort, Randall J Olsen, James M Musser, Muthiah Kumaraswami
Successful pathogens use complex signaling mechanisms to monitor their environment and reprogram global gene expression during specific stages of infection. Group A Streptococcus (GAS) is a major human pathogen that causes significant disease burden worldwide. A secreted cysteine protease known as streptococcal pyrogenic exotoxin B (SpeB) is a key virulence factor that is produced abundantly during infection and is critical for GAS pathogenesis. Although identified nearly a century ago, the molecular basis for growth phase control of speB gene expression remains unknown...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
A Di Matteo, M Franceschini, A Paiardini, A Grottesi, S Chiarella, S Rocchio, C Di Natale, D Marasco, L Vitagliano, C Travaglini-Allocatelli, L Federici
Nucleophosmin (NPM1) is a multifunctional nucleolar protein implicated in ribogenesis, centrosome duplication, cell cycle control, regulation of DNA repair and apoptotic response to stress stimuli. The majority of these functions are played through the interactions with a variety of protein partners. NPM1 is frequently overexpressed in solid tumors of different histological origin. Furthermore NPM1 is the most frequently mutated protein in acute myeloid leukemia (AML) patients. Mutations map to the C-terminal domain and lead to the aberrant and stable localization of the protein in the cytoplasm of leukemic blasts...
September 18, 2017: Oncogenesis
Cheah Wen Yapp, Amal Widaad Mohaimin, Adi Idris
BACKGROUND: Cytosolic double-stranded RNA (dsRNA) is an important 'molecular signature' for the detection of intracellular viral infections. Although intracellular dsRNA is a known potent inducer of apoptosis, the optimal time and dose for the onset of dsRNA-mediated apoptosis have not been studied in detail. OBJECTIVE: To perform an accurate temporal assessment of the cell death responses in dsRNA-dependent cytotoxicity. METHODS: Poly I:C (PIC), a synthetic dsRNA molecule was delivered intracellularly into J774...
September 2017: Iranian Journal of Immunology: IJI
Carsten Schmuck, Sandra Junghänel, Sarah Karczewski, Sandra Bäcker, Shirley Knauer
We discovered a new class of artificial peptidic transfection vectors based on an artificial anion binding motif, the guanidiniocarbonylpyrrole cation (abbreviated as GCP). This new type of vector is surprisingly small compared to traditional systems and our previous work suggested that the GCP group is important for promoting the critical endosomal escape. We now present here a systematic comparison of similar DNA-ligands featuring our GCP oxo-anion binding motif with DNA-ligands only consisting of natural occurring amino acids...
September 15, 2017: Chembiochem: a European Journal of Chemical Biology
James T DeLigio, Grace Lin, Charles E Chalfant, Margaret A Park
The translational regulator cytosolic polyadenylation element binding protein 2 has two isoforms, CPEB2A and CPEB2B, derived by alternative splicing of RNA into a mature form that either includes or excludes exon 4. Previously, we reported that this splicing event is highly dysregulated in aggressive forms of breast cancers, which overexpress CPEB2B. The loss of CPEB2A with a concomitant increase in CPEB2B was also required for breast cancer cells to resist cell death due to detachment (anoikis resistance) and metastasize in vivo...
September 13, 2017: Journal of Biological Chemistry
Liudmila Andreeva, Björn Hiller, Dirk Kostrewa, Charlotte Lässig, Carina C de Oliveira Mann, David Jan Drexler, Andreas Maiser, Moritz Gaidt, Heinrich Leonhardt, Veit Hornung, Karl-Peter Hopfner
Cytosolic DNA arising from intracellular pathogens triggers a powerful innate immune response. It is sensed by cyclic GMP-AMP synthase (cGAS), which elicits the production of type I interferons by generating the second messenger 2'3'-cyclic-GMP-AMP (cGAMP). Endogenous nuclear or mitochondrial DNA can also be sensed by cGAS under certain conditions, resulting in sterile inflammation. The cGAS dimer binds two DNA ligands shorter than 20 base pairs side-by-side, but 20-base-pair DNA fails to activate cGAS in vivo and is a poor activator in vitro...
September 13, 2017: Nature
Judit Danis, Anikó Göblös, Zsuzsanna Bata-Csörgő, Lajos Kemény, Márta Széll
Cytosolic DNA fragments are recognized as pathogen- and danger-associated molecular patterns that induce a cascade of innate immune responses. Moreover, excessive cytosolic DNA can enhance chronic inflammation, predominantly by activating inflammasomes, and thereby contributing to the pathogenesis of chronic diseases, such as psoriasis. Psoriasis associated non-protein coding RNA induced by stress (PRINS) is a long non-coding RNA, which has been shown to be associated with psoriasis susceptibility and cellular stress responses; however, the precise mechanism of its action has not been determined...
2017: Frontiers in Immunology
Patrick Midoux, Lucie Pigeon, Cristine Gonçalves, Chantal Pichon
Synthetic vectors such as cationic polymers and cationic lipids remain attractive tools for non-viral gene transfer which is a complex process whose effectiveness relies on the ability to deliver a plasmid DNA (pDNA) into the nucleus of non-dividing cells. Once in the cytosol, the transport of pDNAs towards the nuclear envelop is strongly impaired by their very low cytosolic mobility due to their large size. To promote their movement towards the cell nucleus, few strategies have been implemented to exploit dynein, the microtubule's motor protein, for propagation of cytosolic pDNA along the microtubules (MTs) towards the cell nucleus...
September 12, 2017: Bioscience Reports
Bradley S Gordon, Jennifer L Steiner, Michael L Rossetti, Shuxi Qiao, Leif W Ellisen, Subramaniam S Govindarajan, Alexey M Eroshkin, Dave L Williamson, Paul M Coen
The metabolic stress placed on skeletal muscle by aerobic exercise promotes acute and long-term health benefits in part through changes in gene expression. However, the transducers that mediate altered gene expression signatures have not been completely elucidated. Regulated in Development and DNA Damage 1 (REDD1) is a stress-induced protein whose expression is transiently increased in skeletal muscle following acute aerobic exercise. However, the role of this induction remains unclear. Because REDD1 altered gene expression in other model systems, we sought to determine whether REDD1 induction following acute exercise altered the gene expression signature in muscle...
September 12, 2017: American Journal of Physiology. Endocrinology and Metabolism
Xiao-Xia Du, Xiao-Dong Su
STING (stimulator of interferon genes) is an essential signaling adaptor protein mediating cytosolic DNA-induced innate immunity for both microbial invasion and self-DNA leakage. STING is also a direct receptor for cytosolic cyclic dinucleotides (CDNs), including the microbial secondary messengers c-di-GMP (3',3'-cyclic di-GMP), 3',3'cGAMP (3',3'-cyclic GMP-AMP), and mammalian endogenous 2',3'cGAMP (2',3'-cyclic GMP-AMP) synthesized by cGAS (cyclic GMP-AMP synthase). Upon CDN binding, STING undergoes a conformational change to enable signal transduction by phosphorylation and finally to active IRF3 (Interferon regulatory factor 3) for type I interferon production...
2017: Methods in Molecular Biology
Christine Wachnowsky, James A Cowan
Iron-sulfur clusters are metal cofactors that comprise the largest class of metalloproteins and are utilized for a wide variety of functions ranging from electron transport to DNA repair. These clusters and their respective cluster-binding proteins are highly conserved and are produced in the mitochondria via an evolutionarily conserved process for export to the cytosol and delivery to other organelles, including the nucleus. Disruption of the biosynthetic pathway results in a number of disease conditions that reflect the essential requirements of cluster function and trafficking within the cell...
2017: Methods in Enzymology
Veysel T Yilmaz, Ceyda Icsel, Jenaidullah Batur, Seyma Aydinlik, Pinar Sahinturk, Muhittin Aygun
New silver(I) 5,5-diethylbarbiturate (barb) complexes with a series of bis(diphenylphosphino)alkanes such as 1,1-bis(diphenylphosphino)methane (dppm), 1,2-bis(diphenylphosphino)ethane (dppe), 1,3-bis(diphenylphosphino)propane (dppp) and 1,4-bis(diphenylphosphino)butane (dppb) were synthesized and characterized. [Ag2(barb)2(μ-dppm)2] (1), [Ag2(barb)2(μ-dppe)(DMSO)2] (2) and [Ag2(barb)2(μ-dppp)2] (3) were binuclear, while [Ag(barb)(μ-dppb)]n (4) was a coordination polymer. 1-4 effectively bind to the G/C rich region of the major groove of DNA and interact with BSA via hydrophobic interactions in accordance with molecular docking studies...
August 31, 2017: European Journal of Medicinal Chemistry
Muhammet F Gulen, Ute Koch, Simone M Haag, Fabian Schuler, Lionel Apetoh, Andreas Villunger, Freddy Radtke, Andrea Ablasser
Mammalian cells use cytosolic nucleic acid receptors to detect pathogens and other stress signals. In innate immune cells the presence of cytosolic DNA is sensed by the cGAS-STING signalling pathway, which initiates a gene expression programme linked to cellular activation and cytokine production. Whether the outcome of the STING response varies between distinct cell types remains largely unknown. Here we show that T cells exhibit an intensified STING response, which leads to the expression of a distinct set of genes and results in the induction of apoptosis...
September 5, 2017: Nature Communications
Aaron M Tocker, Emily Durocher, Kimberly D Jacob, Kate E Trieschman, Suzanna M Talento, Alma A Rechnitzer, David M Roberts, Beckley K Davis
Sensing of cytosolic nucleotides is a critical initial step in the elaboration of type I IFN. One of several upstream receptors, cyclic GMP-AMP synthase, binds to cytosolic DNA and generates dicyclic nucleotides that act as secondary messengers. These secondary messengers bind directly to stimulator of IFN genes (STING). STING recruits TNFR-associated NF-κB kinase-binding kinase 1 which acts as a critical node that allows for efficient activation of IFN regulatory factors to drive the antiviral transcriptome...
September 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
S Gauthami, Deepak Kumar, K S R SivaSai, Nagendra R Hegde
Biotinylation has been extensively used for antibody tagging, affinity-based purification, and in protein/DNA-protein interaction studies. Here we describe the use of biotinylation to study the turn-over of proteins in cells. We use the prokaryotic biotin ligase (BirA) to biotinylate the human leukocyte antigen (HLA)-A2 (A2) heavy chain (HC), which was engineered to contain a biotin acceptor peptide (BAP). Controlled availability of biotin in combination with visualization using streptavidin-conjugated peroxidase made it possible to detect biotinylated BAP-A2...
August 30, 2017: Immunology Letters
Marina Ruiz de Galarreta, Amaia Lujambio
Cellular senescence, a cell-autonomous growth arrest program, also executes pleiotropic non-cell-autonomous activities through the senescence-associated secretory phenotype (SASP). The innate cGAS-STING DNA-sensing pathway is now shown to regulate senescence by recognizing cytosolic DNA and inducing SASP factors, uncovering an unexpected link between these two previously unrelated pathways.
August 31, 2017: Nature Cell Biology
Shuzhen Li, Zhenzhen Sun, Guixia Ding, Wei Gong, Jing Yu, Weiwei Xia, Songming Huang, Aihua Zhang, Yue Zhang, Zhanjun Jia
BACKGROUND/AIMS: We previously reported that indoxyl sulfate (IS) could cause mesangial cell (MC) proliferation via a cyclooxygenase (COX)-2-dependent mechanism. However, the specific prostaglandin contributing to COX-2 effect on IS-induced MC proliferation remained unknown. Thus, the present study was undertaken to examine the role of microsomal prostaglandin E synthase-1 (mPGES-1)-derived Prostaglandin E2 (PGE2) in IS-induced MC proliferation. METHODS: IS was administered to the MCs with or without mPGES-1 siRNA pretreatment to induce the MC proliferation which was determined by cell cycle analysis, DNA synthesis, and the expressions of cyclins...
August 30, 2017: Cellular Physiology and Biochemistry
Felix Kraus, Michael T Ryan
A key event in the evolution of eukaryotic cells was the engulfment of an aerobic bacterium by a larger anaerobic archaebacterium, leading to a close relationship between the host and the newly formed endosymbiont. Mitochondria, originating from this event, have evolved to be the main place of cellular ATP production. Maintaining elements of their independence, mitochondria undergo growth and division in the cell, thereby ensuring that new daughter cells inherit a mitochondrial complement. Mitochondrial division is also important for other processes, including quality control, mitochondrial (mt)DNA inheritance, transport and cell death...
August 25, 2017: Journal of Cell Science
Roberta Cascella, Giulia Fani, Claudia Capitini, Paola Rusmini, Angelo Poletti, Cristina Cecchi, Fabrizio Chiti
Amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions are neurodegenerative disorders that share the cytosolic deposition of TDP-43 (TAR DNA-binding protein 43) in the CNS. TDP-43 is well known as being actively degraded by both the proteasome and macroautophagy. The well-documented decrease in the efficiency of these clearance systems in aging and neurodegeneration, as well as the genetic evidence that many of the familial forms of TDP-43 proteinopathies involve genes that are associated with them, suggest that a failure of these protein degradation systems is a major factor that contributes to the onset of TDP-43-associated disorders...
August 25, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Cathrine Elisabeth Olsen, Simen Sellevold, Theodossis Theodossiou, Sebastian Patzke, Kristian Berg
The low curative response to current treatment regimens for most soft tissue sarcomas indicates a strong need for alternative treatment strategies and predictive markers for treatment outcome. PCI (photochemical internalization) is a novel treatment strategy to translocate drugs into cytosol that otherwise would have been degraded in lysosomes. Two highly geno-and phenotypically different uterine and vulvar leiomyosarcoma cell lines, MES-SA and SK-LMS-1, were treated with bleomycin (BLM) activated by PCI (PCIBLM)...
August 21, 2017: Photodiagnosis and Photodynamic Therapy
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