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https://www.readbyqxmd.com/read/28821810/extracting-intercellular-signaling-network-of-cancer-tissues-using-ligand-receptor-expression-patterns-from-whole-tumor-and-single-cell-transcriptomes
#1
Joseph X Zhou, Roberto Taramelli, Edoardo Pedrini, Theo Knijnenburg, Sui Huang
Many behaviors of cancer, such as progression, metastasis and drug resistance etc., cannot be fully understood by genetic mutations or intracellular signaling alone. Instead, they are emergent properties of the cell community which forms a tumor. Studies of tumor heterogeneity reveal that many cancer behaviors critically depend on intercellular communication between cancer cells themselves and between cancer-stromal cells by secreted signaling molecules (ligands) and their cognate receptors. We analyzed public cancer transcriptome database for changes in cell-cell interactions as the characteristic of malignancy...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28820292/p53-binding-sites-in-normal-and-cancer-cells-are-characterized-by-distinct-chromatin-context
#2
Feifei Bao, Peter R LoVerso, Jeffrey N Fisk, Victor B Zhurkin, Feng Cui
The tumor suppressor protein p53 interacts with DNA in a sequence-dependent manner. Thousands of p53 binding sites have been mapped genome-wide in normal and cancer cells. However, the way p53 selectively binds its cognate sites in different types of cells is not fully understood. Here, we performed a comprehensive analysis of 25 published p53 cistromes and identified 3,551 and 6,039 'high-confidence' binding sites in normal and cancer cells, respectively. Our analysis revealed two distinct epigenetic features underlying p53-DNA interactions in vivo...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28808054/mst4-phosphorylates-acap4-to-orchestrate-apical-membrane-remodeling-during-gastric-acid-secretion
#3
Xiao Yuan, Phil Y Yao, Jiying Jiang, Yin Zhang, Zeqi Su, Wendy Yao, Xueying Wang, Ping Gui, McKay Mullen, Calmour Henry, Tarsha Ward, Wenwen Wang, Larry Brako, Ruijun Tian, Xuannv Zhao, Fengsong Wang, Xinwang Cao, Dongmei Wang, Xing Liu, Xia Ding, Xuebiao Yao
The digestion in the stomach depends on acidification of the lumen. Histamine-elicited acid secretion is triggered by activation of PKA cascade, which ultimately results in the insertion of gastric H,K-ATPases into the apical plasma membranes of parietal cells. Our recent study revealed the functional role of PKA-MST4-ezrin signaling axis in histamine-elicited acid secretion (Jiang et al., 2015. J. Biol. Chem. 290, 28272-28285). However, it remains uncharacterized how PKA-MST4-ezrin signaling axis operates the insertion of H,K-ATPases into the apical plasma membranes of gastric parietal cells...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28716922/local-destabilization-rigid-body-and-fuzzy-docking-facilitate-the-phosphorylation-of-the-transcription-factor-ets-1-by-the-mitogen-activated-protein-kinase-erk2
#4
Andrea Piserchio, Mangalika Warthaka, Tamer S Kaoud, Kari Callaway, Kevin N Dalby, Ranajeet Ghose
Mitogen-activated protein (MAP) kinase substrates are believed to require consensus docking motifs (D-site, F-site) to engage and facilitate efficient site-specific phosphorylation at specific serine/threonine-proline sequences by their cognate kinases. In contrast to other MAP kinase substrates, the transcription factor Ets-1 has no canonical docking motifs, yet it is efficiently phosphorylated by the MAP kinase ERK2 at a consensus threonine site (T38). Using NMR methodology, we demonstrate that this phosphorylation is enabled by a unique bipartite mode of ERK2 engagement by Ets-1 and involves two suboptimal noncanonical docking interactions instead of a single canonical docking motif...
August 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28656904/mapping-quorum-sensing-onto-neural-networks-to-understand-collective-decision-making-in-heterogeneous-microbial-communities
#5
Tahir I Yusufaly, James Q Boedicker
Microbial communities frequently communicate via quorum sensing (QS), where cells produce, secrete, and respond to a threshold level of an autoinducer (AI) molecule, thereby modulating gene expression. However, the biology of QS remains incompletely understood in heterogeneous communities, where variant bacterial strains possess distinct QS systems that produce chemically unique AIs. AI molecules bind to 'cognate' receptors, but also to 'non-cognate' receptors found in other strains, resulting in inter-strain crosstalk...
July 19, 2017: Physical Biology
https://www.readbyqxmd.com/read/28611094/agonist-specific-protein-interactomes-of-glucocorticoid-and-androgen-receptor-as-revealed-by-proximity-mapping
#6
Joanna K Lempiäinen, Einari A Niskanen, Kaisa-Mari Vuoti, Riikka E Lampinen, Helka Göös, Markku Varjosalo, Jorma J Palvimo
Glucocorticoid receptor (GR) and androgen receptor (AR) are steroid-inducible transcription factors (TFs). The GR and the AR are central regulators of various metabolic, homeostatic and differentiation processes and hence important therapeutic targets, especially in inflammation and prostate cancer, respectively. Hormone binding to these steroid receptors (SRs) leads to DNA binding and activation or repression of their target genes with the aid of interacting proteins, coregulators. However, protein interactomes of these important drug targets have remained poorly defined...
August 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28607033/perception-of-root-active-cle-peptides-requires-coryne-function-in-the-phloem-vasculature
#7
Ora Hazak, Benjamin Brandt, Pietro Cattaneo, Julia Santiago, Antia Rodriguez-Villalon, Michael Hothorn, Christian S Hardtke
Arabidopsis root development is orchestrated by signaling pathways that consist of different CLAVATA3/EMBRYO SURROUNDING REGION (CLE) peptide ligands and their cognate CLAVATA (CLV) and BARELY ANY MERISTEM (BAM) receptors. How and where different CLE peptides trigger specific morphological or physiological changes in the root is poorly understood. Here, we report that the receptor-like protein CLAVATA 2 (CLV2) and the pseudokinase CORYNE (CRN) are necessary to fully sense root-active CLE peptides. We uncover BAM3 as the CLE45 receptor in the root and biochemically map its peptide binding surface...
August 2017: EMBO Reports
https://www.readbyqxmd.com/read/28600003/novel-insights-into-the-expression-pattern-of-anaphylatoxin-receptors-in-mice-and-men
#8
Yves Laumonnier, Christian M Karsten, Jörg Köhl
The anaphylatoxins (AT) C3a and C5a play important roles as mediators of inflammation. Further, they regulate and control multiple innate and adaptive immune responses through binding and activation of their cognate G protein-coupled receptors, i.e. C3a receptor (C3aR), C5a receptor 1 (C5aR1) and C5a receptor 2 (C5aR2), although the latter lacks important sequence motifs for G protein-coupling. Based on their pleiotropic functions, they contribute not only to tissue homeostasis but drive, perpetuate and resolve immune responses in many inflammatory diseases including infections, malignancies, autoimmune as well as allergic diseases...
June 6, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28481982/mcpas-tcr-a-manually-curated-catalogue-of-pathology-associated-t-cell-receptor-sequences
#9
Nili Tickotsky, Tal Sagiv, Jaime Prilusky, Eric Shifrut, Nir Friedman
Motivation: While growing numbers of T cell receptor (TCR) repertoires are being mapped by high-throughput sequencing, existing methods do not allow for computationally connecting a given TCR sequence to its target antigen, or relating it to a specific pathology. As an alternative, a manually-curated database can relate TCR sequences with their cognate antigens and associated pathologies based on published experimental data. Results: We present McPAS-TCR, a manually curated database of TCR sequences associated with various pathologies and antigens based on published literature...
May 8, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28422494/genetically-encoded-2-aryl-5-carboxytetrazoles-for-site-selective-protein-photo-cross-linking
#10
Yulin Tian, Marco Paolo Jacinto, Yu Zeng, Zhipeng Yu, Jun Qu, Wenshe R Liu, Qing Lin
The genetically encoded photo-cross-linkers promise to offer a temporally controlled tool to map transient and dynamic protein-protein interaction complexes in living cells. Here we report the synthesis of a panel of 2-aryl-5-carboxytetrazole-lysine analogs (ACTKs) and their site-specific incorporation into proteins via amber codon suppression in Escherichia coli and mammalian cells. Among five ACTKs investigated, N-methylpyrroletetrazole-lysine (mPyTK) was found to give robust and site-selective photo-cross-linking reactivity in E...
May 3, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28417191/mapping-of-estradiol-binding-sites-through-receptor-micro-autoradiography-in-the-endometrial-stroma-of-early-pregnant-mice
#11
Telma M T Zorn, Rodolfo R Favaro, Mauricio Soto-Suazo, Walter E Stumpf
Estradiol triggers key biological responses in the endometrium, which rely on the presence and levels of its cognate receptors on target cells. Employing the receptor micro-autoradiography (RMAR) technique, we aimed to provide a temporal and spatial map of the functional binding sites for estradiol in the mouse endometrial stroma during early pregnancy. Uterine samples from days 1.5 to 7.5 of pregnancy were collected 1 h after tritiated- (3H-) estradiol administration and prepared for RMAR analysis. Autoradiographic incorporation of 3H-thymidine (after 1-h pulse) was evaluated over the same gestational interval...
September 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28344190/an-artificial-intelligence-approach-fit-for-trna-gene-studies-in-the-era-of-big-sequence-data
#12
Yuki Iwasaki, Takashi Abe, Kennosuke Wada, Yoshiko Wada, Toshimichi Ikemura
Unsupervised data mining capable of extracting a wide range of knowledge from big data without prior knowledge or particular models is a timely application in the era of big sequence data accumulation in genome research. By handling oligonucleotide compositions as high-dimensional data, we have previously modified the conventional self-organizing map (SOM) for genome informatics and established BLSOM, which can analyze more than ten million sequences simultaneously. Here, we develop BLSOM specialized for tRNA genes (tDNAs) that can cluster (self-organize) more than one million microbial tDNAs according to their cognate amino acid solely depending on tetra- and pentanucleotide compositions...
March 24, 2017: Genes & Genetic Systems
https://www.readbyqxmd.com/read/28336542/seten-a-tool-for-systematic-identification-and-comparison-of-processes-phenotypes-and-diseases-associated-with-rna-binding-proteins-from-condition-specific-clip-seq-profiles
#13
Gungor Budak, Rajneesh Srivastava, Sarath Chandra Janga
RNA-binding proteins (RBPs) control the regulation of gene expression in eukaryotic genomes at post-transcriptional level by binding to their cognate RNAs. Although several variants of CLIP (crosslinking and immunoprecipitation) protocols are currently available to study the global protein-RNA interaction landscape at single-nucleotide resolution in a cell, currently there are very few tools that can facilitate understanding and dissecting the functional associations of RBPs from the resulting binding maps...
June 2017: RNA
https://www.readbyqxmd.com/read/28318499/loss-of-function-mutations-in-lgi4-a-secreted-ligand-involved-in-schwann-cell-myelination-are-responsible-for-arthrogryposis-multiplex-congenita
#14
Shifeng Xue, Jérôme Maluenda, Florent Marguet, Mohammad Shboul, Loïc Quevarec, Carine Bonnard, Alvin Yu Jin Ng, Sumanty Tohari, Thong Teck Tan, Mung Kei Kong, Kristin G Monaghan, Megan T Cho, Carly E Siskind, Jacinda B Sampson, Carolina Tesi Rocha, Fawaz Alkazaleh, Marie Gonzales, Luc Rigonnot, Sandra Whalen, Marta Gut, Ivo Gut, Martine Bucourt, Byrappa Venkatesh, Annie Laquerrière, Bruno Reversade, Judith Melki
Arthrogryposis multiplex congenita (AMC) is a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. Through genetic mapping of disease loci and whole-exome sequencing in four unrelated multiplex families presenting with severe AMC, we identified biallelic loss-of-function mutations in LGI4 (leucine-rich glioma-inactivated 4). LGI4 is a ligand secreted by Schwann cells that regulates peripheral nerve myelination via its cognate receptor ADAM22 expressed by neurons...
April 6, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28105698/characterization-and-in-vivo-regulon-determination-of-an-ecf-sigma-factor-and-its-cognate-anti-sigma-factor-in-nostoc-punctiforme
#15
Nicole Bell, Jamie J Lee, Michael L Summers
Based on primary sequence comparisons and genomic context, Npun_F4153 (SigG)/Npun_F4154 (SapG) of the cyanobacterium Nostoc punctiforme were hypothesized to encode an ECF sigma factor/anti-sigma factor pair. Transcription of sigG increased in heterocysts and akinetes, and after EDTA treatment. Interaction between SigG and the predicted cytoplasmic domain of SapG was observed in vitro. A SigG-GFP translational fusion protein localized to the periphery of vegetative cells in vivo, but lost this association following heat stress...
April 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28026090/the-mesenchymal-precursor-cell-marker-antibody-stro-1-binds-to-cell-surface-heat-shock-cognate-70
#16
Stephen Fitter, Stan Gronthos, Soo Siang Ooi, Andrew C W Zannettino
Since its discovery more than 25 years ago, the STRO-1 antibody has played a fundamental role in defining the hierarchical nature of mesenchymal precursor cells (MPC) and their progeny. STRO-1 antibody binding remains a hallmark of immature pluripotent MPC. Despite the significance of STRO-1 in the MPC field, the identity of the antigen has remained elusive. Using a combination of two-dimensional gel electrophoresis, coupled with Western blotting and Tandem mass spectroscopy, we have identified the STRO-1 antigen as heat shock cognate 70 (HSC70;HSPA8)...
December 27, 2016: Stem Cells
https://www.readbyqxmd.com/read/28004095/epitope-mapping-of-mono-and-polyclonal-antibodies-by-screening-phage-displayed-random-peptide-libraries
#17
Peter Molek, Tomaž Bratkovič
Detailed knowledge of antigenic determinants is crucial when characterizing therapeutic and diagnostic antibodies, assessing vaccine effectiveness and developing epitope-based vaccines. Most epitope mapping approaches are labor intensive and costly. In this study, we evaluated panning of phage-displayed random peptide libraries against antibodies as a tool for cognate epitope identification. We used six antibodies directed to three model protein antigens as targets to show that the approach is applicable to both mono- and polyclonal antibodies...
December 2016: Acta Chimica Slovenica
https://www.readbyqxmd.com/read/27978489/structural-mutational-and-biophysical-studies-reveal-a-canonical-mode-of-molecular-recognition-between-immune-receptor-tigit-and-nectin-2
#18
Dibyendu Samanta, Haisu Guo, Rotem Rubinstein, Udupi A Ramagopal, Steven C Almo
In addition to antigen-specific stimulation of T cell receptor (TCR) by a peptide-MHC complex, the functional outcome of TCR engagement is regulated by antigen-independent costimulatory signals. Costimulatory signals are provided by an array of interactions involving activating and inhibitory receptors expressed on T cells and their cognate ligands on antigen presenting cells. T cell immunoglobulin and ITIM domain (TIGIT), a recently identified immune receptor expressed on T and NK cells, upon interaction with either of its two ligands, nectin-2 or poliovirus receptor (PVR), inhibits activation of T and NK cells...
January 2017: Molecular Immunology
https://www.readbyqxmd.com/read/27935141/evolution-of-a-multi-step-phosphorelay-signal-transduction-system-in-ensifer-recruitment-of-the-sigma-factor-rpon-and-a-novel-enhancer-binding-protein-triggers-acid-activated-gene-expression
#19
Rui Tian, Stephan Heiden, Wan A M Osman, Julie K Ardley, Euan K James, Margaret M Gollagher, Ravi Tiwari, Rekha Seshadri, Nikos C Kyrpides, Wayne G Reeve
Most Ensifer strains are comparatively acid sensitive, compromising their persistence in low pH soils. In the acid-tolerant strain Ensifer medicae WSM419, the acid-activated expression of lpiA is essential for enhancing survival in lethal acidic conditions. Here we characterise a multi-step phosphorelay signal transduction pathway consisting of TcsA, TcrA, FsrR, RpoN and its cognate enhancer-binding protein EbpA, which is required for the induction of lpiA and the downstream acvB gene. The fsrR, tcrA, tcsA and rpoN genes were constitutively expressed, whereas lpiA and acvB were strongly acid-induced...
December 9, 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/27935041/avrpm2-encodes-an-rnase-like-avirulence-effector-which-is-conserved-in-the-two-different-specialized-forms-of-wheat-and-rye-powdery-mildew-fungus
#20
Coraline R Praz, Salim Bourras, Fansong Zeng, Javier Sánchez-Martín, Fabrizio Menardo, Minfeng Xue, Lijun Yang, Stefan Roffler, Rainer Böni, Gerard Herren, Kaitlin E McNally, Roi Ben-David, Francis Parlange, Simone Oberhaensli, Simon Flückiger, Luisa K Schäfer, Thomas Wicker, Dazhao Yu, Beat Keller
There is a large diversity of genetically defined resistance genes in bread wheat against the powdery mildew pathogen Blumeria graminis (B. g.) f. sp. tritici. Many confer race-specific resistance to this pathogen, but until now only the mildew avirulence gene AvrPm3(a2/f2) that is recognized by Pm3a/f was known molecularly. We performed map-based cloning and genome-wide association studies to isolate a candidate for the mildew avirulence gene AvrPm2. We then used transient expression assays in Nicotiana benthamiana to demonstrate specific and strong recognition of AvrPm2 by Pm2...
February 2017: New Phytologist
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