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https://www.readbyqxmd.com/read/29594759/mcp-1-is-overexpressed-in-triple-negative-breast-cancers-and-drives-cancer-invasiveness-and-metastasis
#1
Pranabananda Dutta, Marianna Sarkissyan, Kimberly Paico, Yanyuan Wu, Jaydutt V Vadgama
BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer that lacks ER/PR and HER2 receptors. Hence, there is urgency in developing new or novel therapeutic strategies for treatment of TNBC. Our study shows that the Monocyte Chemoattractant Protein-1 (MCP-1) is a marker associated with TNBC and may play a key role in TNBC disease progression. EXPERIMENTAL DESIGN: ELISA method was used to measure secreted MCP-1, and mRNA levels were determined by Real-time PCR in numerous cancer cell lines, representing various breast cancer subtypes...
March 28, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29563167/genome-wide-determinants-of-sequence-specific-dna-binding-of-general-regulatory-factors
#2
Matthew J Rossi, William K M Lai, B Franklin Pugh
General regulatory factors (GRFs), such as Reb1, Abf1, Rap1, Mcm1, and Cbf1, positionally organize yeast chromatin through interactions with a core consensus DNA sequence. It is assumed that sequence recognition via direct base readout suffices for specificity and that spurious nonfunctional sites are rendered inaccessible by chromatin. We tested these assumptions through genome-wide mapping of GRFs in vivo and in purified biochemical systems at near-base pair (bp) resolution using several ChIP-exo-based assays...
March 21, 2018: Genome Research
https://www.readbyqxmd.com/read/29457883/mapping-the-h-nox-hk-binding-interface-in-vibrio-cholerae-by-hydrogen-deuterium-exchange-mass-spectrometry
#3
Yirui Guo, Anthony T Iavarone, Matthew M Cooper, Michael A Marletta
Heme-nitric oxide/oxygen binding (H-NOX) proteins are a group of hemoproteins that bind diatomic gas ligands such as nitric oxide (NO) and oxygen (O2 ). H-NOX proteins typically regulate histidine kinases (HK) located within the same operon. It has been reported that NO-bound H-NOXs inhibit cognate histidine kinase autophosphorylation in bacterial H-NOX/HK complexes, however, a detailed mechanism of NO-mediated regulation of the H-NOX/HK activity remains unknown. In this study, the binding interface of Vibrio cholerae (Vc) H-NOX/HK complex was characterized by hydrogen/deuterium exchange mass spectrometry (HDX-MS) and further validated by mutagenesis, leading to a new model for NO-dependent kinase inhibition...
February 19, 2018: Biochemistry
https://www.readbyqxmd.com/read/29456874/a-novel-approach-to-data-collection-for-difficult-structures-data-management-for-large-numbers-of-crystals-with-the-blend-software
#4
Anastasia Mylona, Stephen Carr, Pierre Aller, Isabel Moraes, Richard Treisman, Gwyndaf Evans, James Foadi
The present article describes how to use the computer program BLEND to help assemble complete datasets for the solution of macromolecular structures, starting from partial or complete datasets, derived from data collection from multiple crystals. The program is demonstrated on more than two hundred X-ray diffraction datasets obtained from 50 crystals of a complex formed between the SRF transcription factor, its cognate DNA, and a peptide from the SRF cofactor MRTF-A. This structure is currently in the process of being fully solved...
August 4, 2017: Crystals
https://www.readbyqxmd.com/read/29444108/distribution-of-siderophore-gene-systems-on-a-vibrionaceae-phylogeny-database-searches-phylogenetic-analyses-and-evolutionary-perspectives
#5
Sunniva Katharina Thode, Ewelina Rojek, Mikolaj Kozlowski, Rafi Ahmad, Peik Haugen
Siderophores are small molecules synthesized and secreted by bacteria and fungi to scavenge iron. Extracellular ferri-siderohores are recognized by cognate receptors on the cell surface for transport over membranes. Several siderophore systems from Vibrionaceae representatives are known and well understood, e.g., the molecular structure of the siderophore, the biosynthesis gene cluster and pathway, and the gene expression pattern. Less is known about how these systems are distributed among the ~140 Vibrionaceae species, and which evolutionary processes contributed to the present-day distribution...
2018: PloS One
https://www.readbyqxmd.com/read/29390080/experimental-maps-of-dna-structure-at-nucleotide-resolution-distinguish-intrinsic-from-protein-induced-dna-deformations
#6
Robert N Azad, Dana Zafiropoulos, Douglas Ober, Yining Jiang, Tsu-Pei Chiu, Jared M Sagendorf, Remo Rohs, Thomas D Tullius
Recognition of DNA by proteins depends on DNA sequence and structure. Often unanswered is whether the structure of naked DNA persists in a protein-DNA complex, or whether protein binding changes DNA shape. While X-ray structures of protein-DNA complexes are numerous, the structure of naked cognate DNA is seldom available experimentally. We present here an experimental and computational analysis pipeline that uses hydroxyl radical cleavage to map, at single-nucleotide resolution, DNA minor groove width, a recognition feature widely exploited by proteins...
January 30, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29248493/tnf-%C3%AE-induced-protein-3-tnfaip3-a20-acts-as-a-master-switch-in-tnf-%C3%AE-blockade-driven-il-17a-expression
#7
Paulo C M Urbano, Raúl Aguirre-Gamboa, Angel Ashikov, Bennie van Heeswijk, Anja Krippner-Heidenreich, Henk Tijssen, Yang Li, Valderilio F Azevedo, Lisa J T Smits, Frank Hoentjen, Irma Joosten, Hans J P M Koenen
BACKGROUND: Anti-TNF inhibitors successfully improve the quality of life of patients with inflammatory disease. Unfortunately, not all patients respond to anti-TNF therapy, and some patients show paradoxical immune side effects, which are poorly understood. Surprisingly, anti-TNF agents were shown to promote IL-17A production with as yet unknown clinical implications. OBJECTIVE: We sought to investigate the molecular mechanism underlying anti-TNF-driven IL-17A expression and the clinical implications of this phenomenon...
December 14, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29167281/polytene-chromosome-structure-and-somatic-genome-instability
#8
Allan C Spradling
Polytene chromosomes have for 80 years provided the highest resolution view of interphase genome structure in an animal cell nucleus. These chromosomes represent the normal genomic state of nearly all Drosophila larval and many adult cells, and a better understanding of their striking banded structure has been sought for decades. A more recently appreciated characteristic of Drosophila polytene cells is somatic genome instability caused by unfinished replication (UR). Repair of stalled forks generates enough deletions in polytene salivary gland cells to alter 10%-90% of the DNA strands within more than 100 UR regions comprising 20% of the euchromatic genome...
November 22, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28985404/small-rna-profiling-in-chlamydomonas-insights-into-chloroplast-rna-metabolism
#9
Marina Cavaiuolo, Richard Kuras, Francis-André Wollman, Yves Choquet, Olivier Vallon
In Chlamydomonas reinhardtii, regulation of chloroplast gene expression is mainly post-transcriptional. It requires nucleus-encoded trans-acting protein factors for maturation/stabilization (M factors) or translation (T factors) of specific target mRNAs. We used long- and small-RNA sequencing to generate a detailed map of the transcriptome. Clusters of sRNAs marked the 5' end of all mature mRNAs. Their absence in M-factor mutants reflects the protection of transcript 5' end by the cognate factor. Enzymatic removal of 5'-triphosphates allowed identifying those cosRNA that mark a transcription start site...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28972141/dissecting-the-molecular-assembly-of-the-toxoplasma-gondii-myoa-motility-complex
#10
Cameron J Powell, Meredith L Jenkins, Michelle L Parker, Raghavendran Ramaswamy, Anne Kelsen, David M Warshaw, Gary E Ward, John E Burke, Martin J Boulanger
Apicomplexan parasites such as Toxoplasma gondii rely on a unique form of locomotion known as gliding motility. Generating the mechanical forces to support motility are divergent class XIV myosins (MyoA) coordinated by accessory proteins known as light chains. Although the importance of the MyoA-light chain complex is well-established, the detailed mechanisms governing its assembly and regulation are relatively unknown. To establish a molecular blueprint of this dynamic complex, we first mapped the adjacent binding sites of light chains MLC1 and ELC1 on the MyoA neck (residues 775-818) using a combination of hydrogen-deuterium exchange mass spectrometry and isothermal titration calorimetry...
November 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28833168/effector-mediated-discovery-of-a-novel-resistance-gene-against-bremia-lactucae-in-a-nonhost-lettuce-species
#11
Anne K J Giesbers, Alexandra J E Pelgrom, Richard G F Visser, Rients E Niks, Guido Van den Ackerveken, Marieke J W Jeuken
Candidate effectors from lettuce downy mildew (Bremia lactucae) enable high-throughput germplasm screening for the presence of resistance (R) genes. The nonhost species Lactuca saligna comprises a source of B. lactucae R genes that has hardly been exploited in lettuce breeding. Its cross-compatibility with the host species L. sativa enables the study of inheritance of nonhost resistance (NHR). We performed transient expression of candidate RXLR effector genes from B. lactucae in a diverse Lactuca germplasm set...
November 2017: New Phytologist
https://www.readbyqxmd.com/read/28827308/properties-of-a-family-56-carbohydrate-binding-module-and-its-role-in-the-recognition-and-hydrolysis-of-%C3%AE-1-3-glucan
#12
Andrew Hettle, Alexander Fillo, Kento Abe, Patricia Massel, Benjamin Pluvinage, David N Langelaan, Steven P Smith, Alisdair B Boraston
BH0236 from Bacillus halodurans is a multimodular β-1,3-glucanase comprising an N-terminal family 81 glycoside hydrolase catalytic module, an internal family 6 carbohydrate-binding module (CBM) that binds the nonreducing end of β-1,3-glucan chains, and an uncharacterized C-terminal module classified into CBM family 56. Here, we determined that this latter CBM, BhCBM56, bound the soluble β-1,3-glucan laminarin with a dissociation constant ( Kd ) of ∼26 μm and displayed higher affinity for insoluble β-1,3-glucans with Kd values of ∼2-10 μm but lacked affinity for β-1,3-glucooligosaccharides...
October 13, 2017: Journal of Biological Chemistry
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
#13
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
#14
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 2 distinct epigenetic features underlying p53-DNA interactions in vivo...
2017: Cell Cycle
https://www.readbyqxmd.com/read/28808054/mst4-kinase-phosphorylates-acap4-protein-to-orchestrate-apical-membrane-remodeling-during-gastric-acid-secretion
#15
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
Digestion in the stomach depends on acidification of the lumen. Histamine-elicited acid secretion is triggered by activation of the 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. However, it remains uncharacterized how the PKA-MST4-ezrin signaling axis operates the insertion of H,K-ATPases into the apical plasma membranes of gastric parietal cells...
September 29, 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
#16
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
#17
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
#18
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
#19
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
#20
REVIEW
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...
September 2017: Molecular Immunology
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