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https://www.readbyqxmd.com/read/29149597/structural-basis-for-shelterin-bridge-assembly
#1
Jin-Kwang Kim, Jinqiang Liu, Xichan Hu, Clinton Yu, Kyle Roskamp, Banumathi Sankaran, Lan Huang, Elizabeth A Komives, Feng Qiao
Telomere elongation through telomerase enables chromosome survival during cellular proliferation. The conserved multifunctional shelterin complex associates with telomeres to coordinate multiple telomere activities, including telomere elongation by telomerase. Similar to the human shelterin, fission yeast shelterin is composed of telomeric sequence-specific double- and single-stranded DNA-binding proteins, Taz1 and Pot1, respectively, bridged by Rap1, Poz1, and Tpz1. Here, we report the crystal structure of the fission yeast Tpz1(475-508)-Poz1-Rap1(467-496) complex that provides the structural basis for shelterin bridge assembly...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29149457/hmgb1-controls-liver-cancer-initiation-through-yap-dependent-aerobic-glycolysis
#2
Ruochan Chen, Shan Zhu, Xue-Gong Fan, Haichao Wang, Michael T Lotze, Herbert J Zeh, Timothy R Billiar, Rui Kang, Daolin Tang
Emerging studies have suggested that the Hippo pathway is involved in the tumorigenesis of hepatocellular carcinoma (HCC). However, the key regulator of the Hippo pathway in liver tumor metabolic reprogramming remains elusive. Here, we provide evidence to support that high mobility group box 1 (HMGB1), a chromosomal protein, plays a role in the regulation of the Hippo pathway during liver tumorigenesis. Cre/loxP recombination-mediated HMGB1 depletion in hepatocytes blocks diethylnitrosamine-induced liver cancer initiation in mice, whereas shRNA-mediated gene silencing of HMGB1 inhibits HCC cell proliferation...
November 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29149412/the-translationally-controlled-tumor-protein-and-the-cellular-response-to-ionizing-radiation-induced-dna-damage
#3
Jie Zhang, Grace Shim, Sonia M de Toledo, Edouard I Azzam
The absorption of ionizing radiation by living cells can directly disrupt atomic structures, producing chemical and biological changes. It can also act indirectly through radiolysis of water, thereby generating reactive chemical species that may damage nucleic acids, proteins, and lipids. Together, the direct and indirect effects of radiation initiate a series of biochemical and molecular signaling events that may repair the damage or culminate in permanent physiological changes or cell death. In efforts to gain insight into the mechanisms underlying these effects, we observed a prominent upregulation of the Translationally Controlled Tumor Protein (TCTP) in low dose/low dose rate (137)Cs γ-irradiated cells that was associated with adaptive responses that reduced chromosomal damage to a level lower than what occurs spontaneously...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29149287/genomic-and-epigenomic-immunity-in-common-bean-the-unusual-features-of-nb-lrr-gene-family
#4
Manon M S Richard, Ariane Gratias, Vincent Thareau, Kyung Do Kim, Sandrine Balzergue, Johann Joets, Scott A Jackson, Valérie Geffroy
In plants, a key class of genes comprising most of disease resistance (R) genes encodes Nucleotide-binding leucine-rich repeat (NL) proteins. Access to common bean (Phaseolus vulgaris) genome sequence provides unparalleled insight into the organization and evolution of this large gene family (∼400 NL) in this important crop. As observed in other plant species, most common bean NL are organized in cluster of genes. However, a particularity of common bean is that these clusters are often located in subtelomeric regions close to terminal knobs containing the satellite DNA khipu...
November 15, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/29149170/vibrio-parahaemolyticus-vtra-is-a-membrane-bound-regulator-and-is-activated-via-oligomerization
#5
Ryu Okada, Shigeaki Matsuda, Tetsuya Iida
Vibrio parahaemolyticus is a Gram-negative pathogen that causes food-borne gastroenteritis. A major virulence determinant of the organism is a type III secretion system (T3SS2) encoded on a pathogenicity island, Vp-PAI. Vp-PAI gene expression is regulated by two transcriptional regulators, VtrA and VtrB, whose N-terminal regions share homology with an OmpR-family DNA-binding domain. VtrA activates the gene expression of VtrB, which in turn activates Vp-PAI gene expression; however, the mechanism of this transcriptional activation by VtrA is not well understood...
2017: PloS One
https://www.readbyqxmd.com/read/29148771/an-qm-mm-study-of-the-reaction-catalyzed-by-alkyladenine-dna-glycosylase-examination-of-the-substrate-specificity-of-a-dna-repair-enzyme
#6
Stefan A P Lenz, Stacey D Wetmore
Human alkyladenine DNA glycosylase (AAG) functions as part of the base excision repair pathway to excise structurally diverse oxidized and alkylated DNA purines. Specifically, AAG uses a water molecule activated by a general base and a non-specific active site lined with aromatic residues to cleave the N-glycosidic bond. Despite broad substrate specificity, AAG does not target the natural purines (adenine (A) and guanine (G)). Using the ONIOM(QM:MM) methodology, we provide fundamental atomic level details of AAG bound to DNA-containing a neutral substrate (hypoxanthine (Hx)), a non-substrate (G), or a cationic substrate (7-methylguanine (7MeG)), and probe changes in the reaction pathway that occur when AAG targets different nucleotides...
November 17, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29148722/acoustic-wave-driven-functionalized-particles-for-aptamer-based-target-biomolecule-separation
#7
Raheel Ahmad, Ghulam Destgeer, Muhammad Afzal, Jinsoo Park, Husnain Ahmed, Jin Ho Jung, Kwangseok Park, Tae-Sung Yoon, Hyung Jin Sung
We developed a hybrid microfluidic device that utilized acoustic waves to drive functionalized microparticles inside a continuous flow microchannel and to separate particle-conjugated target proteins from a complex fluid. The acoustofluidic device comprised of an interdigitated transducer (IDT) that produced high-frequency surface acoustic waves (SAW) in a polydimethylsiloxane (PDMS) microfluidic channel. The SAW interacted with the sample fluid flow inside the microchannel and deflected particles from their original streamlines to achieve separation...
November 17, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29148176/differential-proteomic-analysis-reveals-protein-networks-and-pathways-that-may-contribute-to-helicobacter-pylori-fkbp-type-ppiase-associated-gastric-diseases
#8
Yanmei Zhu, Yuehua Gong, Aodi Li, Moye Chen, Dan Kang, Jun Liu, Yuan Yuan
PURPOSE: Though Helicobacter pylori (H. pylori) has been classified as class I carcinogen, key virulence factor generated by H. pylori that causes gastric cancer remains to be fully determined. Recently, we identified a gastric cancer-associated H. pylori gene, peptidylprolyl isomerase-FK506 binding protein (PPIase-FKBP), and showed that PPIase-FKBP was capable of inducing oncogenic transformation of gastric epithelial cells. But its mechanism was unclear. EXPERIMENTAL DESIGN: We carried out a comparative proteomic analysis of human gastric epithelial cells that either express PPIase-FKBP or green fluorescent protein (GFP) using two-dimensional (2-D) gel electrophoresis and then matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS/MS)...
November 16, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/29147905/transcriptional-regulation-of-dj-1
#9
Kazuko Takahashi-Niki, Takeshi Niki, Sanae M M Iguchi-Ariga, Hiroyoshi Ariga
DJ-1 is an oncogene and also a causative gene for familial Parkinson's disease. DJ-1 has various functions, and the oxidative status of a cysteine residue at position 106 (C106) is crucial for determination of the activation level of DJ-1.DJ-1 binds to many proteins, including various transcription factors, and acts as a coactivator or corepressor for regulating their target genes without direct binding to DNA, thereby affecting various cell functions. DJ-1-regulating transcription factors and their modified proteins are the androgen receptor and its regulatory proteins, p53; polypyrimidine tract-binding protein-associated splicing factor (PSF); Keap1, an inhibitor for nuclear factor erythroid2-related factor 2 (Nrf2); sterol regulatory element-binding protein (SREBP); Ras-responsive element-binding protein (RREB1); signal transducer and activator of transcription 1 (STAT1); and Nurr1...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147453/ctla-4-genetic-variants-rs11571317-and-rs3087243-role-in-susceptibility-and-progression-of-breast-cancer
#10
Maruthi Goske, V R Vinish Ramachander, Prasanna Latha Komaravalli, P Fazul Rahman, Chandrasekhar Rao, Parveen Jahan
Background: Dysfunctional regulation at immune checkpoints may lead to escape of the tumor cells and gives a scope to set in the unresolved Breast cancer (BC). The major anti-tumor retort is cell-mediated response which involves T lymphocytes. CTLA-4 (Cytotoxic T lymphocyte associated protein-4) with immune suppressive function and tolerance is associated with various autoimmune diseases and cancers including BC. The present study deals with CTLA-4 gene selected polymorphisms (rs11571317 C/T and rs3087243G/A) to explore their relation with breast cancer susceptibility and progression in BC patients...
October 2017: World Journal of Oncology
https://www.readbyqxmd.com/read/29147009/mitochondrial-uqcrb-as-a-new-molecular-prognostic-biomarker-of-human-colorectal-cancer
#11
Hyun-Chul Kim, Junghwa Chang, Hannah S Lee, Ho Jeong Kwon
Ubiquinol cytochrome c reductase binding protein (UQCRB) is important for mitochondrial complex III stability, electron transport, cellular oxygen sensing and angiogenesis. However, its potential as a prognostic marker in colorectal cancer (CRC) remains unclear. The aim of this study was to determine whether UQCRB can be used as a diagnostic molecular marker for CRC. The correlation between the expression of three genes (UQCRB, UQCRFS1 and MT-CYB) in the mitochondrial respiratory chain complex III and clinico-pathological features was determined...
November 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29146919/nucleosome-acidic-patch-targeting-binuclear-ruthenium-compounds-induce-aberrant-chromatin-condensation
#12
Gabriela E Davey, Zenita Adhireksan, Zhujun Ma, Tina Riedel, Deepti Sharma, Sivaraman Padavattan, Daniela Rhodes, Alexander Ludwig, Sara Sandin, Benjamin S Murray, Paul J Dyson, Curt A Davey
The 'acidic patch' is a highly electronegative cleft on the histone H2A-H2B dimer in the nucleosome. It is a fundamental motif for protein binding and chromatin dynamics, but the cellular impact of targeting this potentially therapeutic site with exogenous molecules remains unclear. Here, we characterize a family of binuclear ruthenium compounds that selectively target the nucleosome acidic patch, generating intra-nucleosomal H2A-H2B cross-links as well as inter-nucleosomal cross-links. In contrast to cisplatin or the progenitor RAPTA-C anticancer drugs, the binuclear agents neither arrest specific cell cycle phases nor elicit DNA damage response, but rather induce an irreversible, anomalous state of condensed chromatin that ultimately results in apoptosis...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146913/autophagy-acts-through-traf3-and-relb-to-regulate-gene-expression-via-antagonism-of-smad-proteins
#13
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/29146583/comparison-of-chip-seq-data-and-a-reference-motif-set-for-human-krab-c2h2-zinc-finger-proteins
#14
Marjan Barazandeh, Sam Lambert, Mihai Albu, Timothy R Hughes
KRAB C2H2 zinc finger proteins (KZNFs) are the largest and most diverse family of human transcription factors, likely due to diversifying selection driven by novel endogenous retroelements (EREs), but the vast majority lack binding motifs or functional data. Two recent studies analyzed a majority of the human KZNFs using either ChIP-seq (60 proteins) or ChIP-exo (221 proteins) in the same cell type (HEK293). The ChIP-exo paper did not describe binding motifs, however. Thirty-nine proteins are represented in both studies, enabling the systematic comparison of the data sets presented here...
November 16, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29146555/extranuclear-signaling-by-sex-steroid-receptors-and-clinical-implications-in-breast-cancer
#15
REVIEW
Viroj Boonyaratanakornkit, Nalo Hamilton, Diana C Márquez-Garbán, Prangwan Pateetin, Eileen M McGowan, Richard J Pietra
Estrogen and progesterone, play essential roles in the development and progression of breast cancer. Over 70% of breast cancers express estrogen receptors (ER) and progesterone receptors (PR), emphasizing the need for better understanding of ER and PR signaling. ER and PR are traditionally viewed as transcription factors and directly bind DNA to regulate gene networks. In addition to nuclear signaling, ER and PR mediate hormone-induced, rapid extranuclear signaling at the cell membrane or in the cytoplasm which initiates downstream signaling to regulate either rapid or extended cellular responses...
November 13, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29146251/differential-protein-dna-contacts-for-activation-and-repression-by-argp-a-lysr-type-lttr-transcriptional-regulator-in-escherichia-coli
#16
Phu Nguyen Le Minh, Cristina Velázquez Ruiz, Steven Vandermeeren, Pamella Abwoyo, Indra Bervoets, Daniel Charlier
ArgP is a LysR-type transcriptional regulator (LTTR) that operates with two effector molecules, lysine and arginine, to differentially regulate gene expression. Effector-free ArgP stimulates transcription of all investigated regulon members, except argO, whereas lysine abolishes this effect. Activation of argO, encoding an exporter for arginine and canavanine, is strictly dependent on arginine-bound ArgP. Lysine counteracts this effect and even though lysine-bound ArgP stimulates RNA polymerase recruitment at the argO promoter, the complex is non-productive...
January 2018: Microbiological Research
https://www.readbyqxmd.com/read/29145633/the-initiation-propagation-and-dynamics-of-crispr-spycas9-r-loop-complex
#17
Yan Zeng, Yang Cui, Yong Zhang, Yanruo Zhang, Meng Liang, Hui Chen, Jie Lan, Guangtao Song, Jizhong Lou
CRISPR-Cas9 system has been widely used for efficient genome editing. Although the structures of Cas9 protein in complex with single-guided RNA (sgRNA) and target DNA have been resolved, the molecular details about the formation of Cas9 endonuclease R-loop structure remain elusive. Here we examine the DNA cleavage activities of Streptococcus pyogenes Cas9 (SpyCas9) and its mutants using various target sequences and study the conformational dynamics of R-loop structure during target binding using single-molecule fluorescence energy transfer (smFRET) technique...
November 14, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29145618/the-histone-variant-h2a-z-promotes-initiation-of-meiotic-recombination-in-fission-yeast
#18
Shintaro Yamada, Kazuto Kugou, Da-Qiao Ding, Yurika Fujita, Yasushi Hiraoka, Hiroshi Murakami, Kunihiro Ohta, Takatomi Yamada
Meiotic recombination is initiated by programmed formation of DNA double strand breaks (DSBs), which are mainly formed at recombination hotspots. Meiotic DSBs require multiple proteins including the conserved protein Spo11 and its cofactors, and are influenced by chromatin structure. For example, local chromatin around hotspots directly impacts DSB formation. Moreover, DSB is proposed to occur in a higher-order chromatin architecture termed 'axis-loop', in which many loops protrude from cohesin-enriched axis...
November 14, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29143375/an-immunoinformatics-approach-to-define-t-cell-epitopes-from-polyketide-and-non-ribosomal-peptide-synthesis-proteins-of-mycobacterium-tuberculosis-as-potential-vaccine-candidates
#19
S Dhivya, V Baskar, S R Kumar, R Sathishkumar
The role of polyketide and non-ribosomal proteins from the class of small molecule metabolism of Mycobacterium tuberculosis is well documented in envelope organization, virulence, and pathogenesis. Consequently, the identification of T cell epitopes from these proteins could serve to define potential antigens for the development of vaccines. Fourty-one proteins from polyketide and non-ribosomal peptide synthesis of small molecule metabolism proteins of M tuberculosis H37Rv were analyzed computationally for the presence of HLA class I binding nanomeric peptides...
November 16, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/29142606/hesperidin-inhibits-ovarian-cancer-cell-viability-through-endoplasmic-reticulum-stress-signaling-pathways
#20
Jun Zhao, Yali Li, Jinfang Gao, Yinshan De
Hesperidin is a vitamin P flavonoid compound primarily present in citrus fruits. The aim of the present study was to investigate whether hesperidin inhibits ovarian cancer cell viability via endoplasmic reticulum stress signaling pathways. A2780 cells were treated with various doses of hesperidin for 6, 12 or 24 h, and the viability of A2780 cells was assessed using the MTT assay. Hesperidin decreased the viability of A2780 cells and increased cytotoxicity in a dose- and time-dependent manner. In addition, hesperidin induced apoptosis and increased cleaved caspase-3 protein expression levels in A2780 cells...
November 2017: Oncology Letters
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