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Ago protein

Matthew J Endsin, Ola Michalec, Lori A Manzon, David A Lovejoy, Richard G Manzon
The corticotropin releasing hormone (CRH) system, which includes the CRH family of peptides, their receptors (CRHRs) and a binding protein (CRHBP), has been strongly conserved throughout vertebrate evolution. The identification of invertebrate homologues suggests this system evolved over 500 million years ago. However, the early vertebrate evolution of the CRH system is not understood. Current theory indicates that Agnathans (hagfishes and lampreys) are monophyletic with a conservative evolution over the past 500 million years and occupy a position at the root of vertebrate phylogeny...
October 21, 2016: General and Comparative Endocrinology
Peter M Fischer
Kinase inhibitor research is a comparatively recent branch of medicinal chemistry and pharmacology and the first small-molecule kinase inhibitor, imatinib, was approved for clinical use only 15 years ago. Since then, 33 more kinase inhibitor drugs have received regulatory approval for the treatment of a variety of cancers and the volume of reports on the discovery and development of kinase inhibitors has increased to an extent where it is now difficult-even for those working in the field-easily to keep an overview of the compounds that are being developed, as currently there are 231 such compounds, targeting 38 different protein and lipid kinases (not counting isoforms), in clinical use or under clinical investigation...
October 24, 2016: Medicinal Research Reviews
Masayuki Yokoi, Fumio Hanaoka
Mammalian cells express two homologs of yeast Rad23, the so-called homolog of Rad23 (HR23) proteins. The HR23 proteins were identified more than two decades ago as factors involved in initiation of global genome nucleotide excision repair (GG-NER) along with their interacting partner, xeroderma pigmentosum group C (XPC) protein. Because the HR23 genes encode proteins harboring ubiquitin-like (UBL) domains at their N-termini and two ubiquitin-associated (UBA) domains in their central- and C-terminal regions, the link between HR23 proteins and proteolytic degradation has been widely explored by several methods, including yeast two-hybrid screening and co-affinity purification...
October 19, 2016: Gene
Jean-Emmanuel Hugonnet, Dominique Mengin-Lecreulx, Alejandro Monton, Tanneke den Blaauwen, Etienne Carbonnelle, Carole Veckerlé, Yves Brun, Michael van Nieuwenhze, Christiane Bouchier, Kuyek Tu, Louis B Rice, Michel Arthur
The target of β-lactam antibiotics is the D,D-transpeptidase activity of penicillin-binding proteins (PBPs) for synthesis of 4→3 cross-links in the peptidoglycan of bacterial cell walls. Unusual 3→3 cross-links formed by L,D-transpeptidases were first detected in Escherichia coli more than four decades ago, however no phenotype has previously been associated with their synthesis. Here we show that production of the L,D-transpeptidase YcbB in combination with elevated synthesis of the (p)ppGpp alarmone by RelA lead to full bypass of the D,D-transpeptidase activity of PBPs and to broad-spectrum β-lactam resistance...
October 21, 2016: ELife
Chantal Brosseau, Mohamed El Oirdi, Ayooluwa Adurogbangba, Xiaofang Ma, Peter Moffett
In plants, RNA silencing regulates gene expression through the action of Dicer-like (DCL) and Argonaute (AGO) proteins via micro RNAs and RNA-dependent DNA methylation (RdDM). In addition, RNA silencing functions as an anti-viral defense mechanism by targeting virus-derived double stranded RNA. Plants encode multiple AGO proteins with specialized functions, including AGO4-like proteins, which effect RdDM and AGO2, AGO5 and AGO1, which have antiviral activities. We show here that AGO4 is also required for defense against Plantago asiatica mosaic potexvirus (PlAMV), most likely independent of RdDM components such as DCL3, Pol IV and Pol V...
October 20, 2016: Molecular Plant-microbe Interactions: MPMI
Adam M Session, Yoshinobu Uno, Taejoon Kwon, Jarrod A Chapman, Atsushi Toyoda, Shuji Takahashi, Akimasa Fukui, Akira Hikosaka, Atsushi Suzuki, Mariko Kondo, Simon J van Heeringen, Ian Quigley, Sven Heinz, Hajime Ogino, Haruki Ochi, Uffe Hellsten, Jessica B Lyons, Oleg Simakov, Nicholas Putnam, Jonathan Stites, Yoko Kuroki, Toshiaki Tanaka, Tatsuo Michiue, Minoru Watanabe, Ozren Bogdanovic, Ryan Lister, Georgios Georgiou, Sarita S Paranjpe, Ila van Kruijsbergen, Shengquiang Shu, Joseph Carlson, Tsutomu Kinoshita, Yuko Ohta, Shuuji Mawaribuchi, Jerry Jenkins, Jane Grimwood, Jeremy Schmutz, Therese Mitros, Sahar V Mozaffari, Yutaka Suzuki, Yoshikazu Haramoto, Takamasa S Yamamoto, Chiyo Takagi, Rebecca Heald, Kelly Miller, Christian Haudenschild, Jacob Kitzman, Takuya Nakayama, Yumi Izutsu, Jacques Robert, Joshua Fortriede, Kevin Burns, Vaneet Lotay, Kamran Karimi, Yuuri Yasuoka, Darwin S Dichmann, Martin F Flajnik, Douglas W Houston, Jay Shendure, Louis DuPasquier, Peter D Vize, Aaron M Zorn, Michihiko Ito, Edward M Marcotte, John B Wallingford, Yuzuru Ito, Makoto Asashima, Naoto Ueno, Yoichi Matsuda, Gert Jan C Veenstra, Asao Fujiyama, Richard M Harland, Masanori Taira, Daniel S Rokhsar
To explore the origins and consequences of tetraploidy in the African clawed frog, we sequenced the Xenopus laevis genome and compared it to the related diploid X. tropicalis genome. We characterize the allotetraploid origin of X. laevis by partitioning its genome into two homoeologous subgenomes, marked by distinct families of 'fossil' transposable elements. On the basis of the activity of these elements and the age of hundreds of unitary pseudogenes, we estimate that the two diploid progenitor species diverged around 34 million years ago (Ma) and combined to form an allotetraploid around 17-18 Ma...
October 19, 2016: Nature
G P Adams, M H Ratto, M E Silva, R A Carrasco
The ovulation-inducing effect of seminal plasma was first reported in Bactrian camels over 30 years ago, and the entity responsible was dubbed 'ovulation-inducing factor' (OIF). More recent studies, primarily in llamas and alpacas, characterized the biological and chemical properties of OIF and ultimately identified it as βNGF. This recent discovery has allowed a convergence of knowledge previously separated by discipline and by mechanism; that is, neurobiology and reproductive biology, and autocrine/paracrine vs endocrine...
October 2016: Reproduction in Domestic Animals, Zuchthygiene
Tripti Sharma, Ingo Dreyer, Leon Kochian, Miguel A Piñeros
About a decade ago, members of a new protein family of anion channels were discovered on the basis of their ability to confer on plants the tolerance toward toxic aluminum ions in the soil. The efflux of Al(3+)-chelating malate anions through these channels is stimulated by external Al(3+) ions. This feature of a few proteins determined the name of the entire protein family as Aluminum-activated Malate Transporters (ALMT). Meanwhile, after several years of research, it is known that the physiological roles of ALMTs go far beyond Al-detoxification...
2016: Frontiers in Plant Science
Immacolata Andolfo, Roberta Russo, Antonella Gambale, Achille Iolascon
After the first proposed model of the red blood cell membrane skeleton 36 years ago, several additional proteins have been discovered during the overriding years, and their relationship with the pathogenesis of the related disorders have been somewhat defined. The knowledge of erythrocyte membrane structure is important because it represents the model for spectrin-based membrane skeletons in all cells and because defects in its structure underlie multiple hemolytic anemias. This review summarized the main features of erythrocyte membrane disorders, dividing them in structural and altered permeability defects, particularly focusing on the most recent advances...
October 18, 2016: Haematologica
Nickias Kienle, Tobias H Kloepper, Dirk Fasshauer
BACKGROUND: A defining feature of eukaryotic cells is the presence of various distinct membrane-bound compartments with different metabolic roles. Material exchange between most compartments occurs via a sophisticated vesicle trafficking system. This intricate cellular architecture of eukaryotes appears to have emerged suddenly, about 2 billion years ago, from much less complex ancestors. How the eukaryotic cell acquired its internal complexity is poorly understood, partly because no prokaryotic precursors have been found for many key factors involved in compartmentalization...
October 18, 2016: BMC Evolutionary Biology
Hilaire C Lam, Julie S Nijmeh, Elizabeth P Henske
In just the past five years, dramatic changes have occurred in the clinical management of Tuberous Sclerosis Complex (TSC). Detailed knowledge about the role of the TSC proteins in regulating the activity of the mammalian Target of Rapamycin Complex 1 (mTORC1) underlies this paradigm-shifting progress. Advances continue to be made in understanding the genetic pathogenesis of the different tumours that occur in TSC, including pivotal discoveries using next-generation sequencing (NGS). For example, the pathogenesis of angiofibromas is now known to involve UV-induced mutations, and the pathogenesis of multifocal renal cell carcinoma (RCC) in TSC is now known to result from distinct second-hit mutations...
October 18, 2016: Journal of Pathology
Jordi Gamir, Rabih Darwiche, Pieter Van't Hof, Vineet Choudhary, Michael Stumpe, Roger Schneiter, Felix Mauch
Pathogenesis-related proteins played a pioneering role fifty years ago in the discovery of plant innate immunity as a set of proteins that accumulated upon pathogen challenge. The most abundant of these proteins, PATHOGENESIS-RELATED 1 (PR-1) encodes a small antimicrobial protein that has become, as a marker of plant immune signaling, one of the most referred to plant proteins. However, the biochemical activity and mode of action of PR-1 proteins has remained elusive. Here, we provide genetic and biochemical evidence for the capacity of PR-1 proteins to bind sterols and demonstrate that the inhibitory effect on pathogen growth is caused by sterol sequestration from pathogens...
October 16, 2016: Plant Journal: for Cell and Molecular Biology
Cindo O Nicholson, Matthew B Friedersdorf, Jack D Keene
RNA-binding proteins (RBPs) and non-coding RNAs orchestrate post-transcriptional processes through the recognition of specific sites on targeted transcripts. Thus, understanding the connection between binding to specific sites and active regulation of the whole transcript is essential. Many immunoprecipitation techniques have been developed that identify either whole transcripts or binding sites of RBPs on each transcript using cell lysates. However, none of these methods simultaneously measures the strength of each binding site, and quantifies binding to whole transcripts...
October 14, 2016: RNA
Sarah Willkomm, Adrian Zander, Dina Grohmann, Tobias Restle
Argonaute (Ago) proteins from all three domains of life are key players in processes that specifically regulate cellular nucleic acid levels. Some of these Ago proteins, among them human Argonaute2 (hAgo2) and Ago from the archaeal organism Methanocaldococcus jannaschii (MjAgo), are able to cleave nucleic acid target strands that are recognised via an Ago-associated complementary guide strand. Here we present an in-depth kinetic side-by-side analysis of hAgo2 and MjAgo guide and target substrate binding as well as target strand cleavage, which enabled us to disclose similarities and differences in the mechanistic pathways as a function of the chemical nature of the substrate...
2016: PloS One
Ryan S D'Souza, James E Casanova
The IQsec/BRAG proteins are a subfamily of Arf-nucleotide exchange factors. Since their discovery almost 15 years ago, the BRAGs have been reported to be involved in diverse physiological processes from myoblast fusion, neuronal pathfinding and angiogenesis, to pathophysiological processes including X-linked intellectual disability and tumor metastasis. In this review we will address how, in each of these situations, the BRAGs are thought to regulate the surface levels of adhesive and signaling receptors. While in most cases BRAGs are thought to enhance the endocytosis of these receptors, how they achieve this remains unclear...
October 14, 2016: Small GTPases
Riccardo Calafiore, Giuseppe Basta, Pia Montanucci
Microencapsulation technology, based on use of alginic acid biopolymers, has been devised many years ago. However, when intended for enveloping human islets for transplantation purposes, the method needs to be up-scaled and implemented with care being taken to comply with simple but important measures. It is almost indispensable to rely on an ultrapurified alginic polymers: in fact, any, even minimal, alginate contamination with endotoxins, pyrogens, and proteins could provoke the host's inflammatory reaction upon graft, with heavy adverse consequences on the capsules immunoprotective properties, hence on graft survival per se...
2017: Methods in Molecular Biology
Marek S Skrzypek, Jonathan Binkley, Gail Binkley, Stuart R Miyasato, Matt Simison, Gavin Sherlock
The Candida Genome Database (CGD, is a freely available online resource that provides gene, protein and sequence information for multiple Candida species, along with web-based tools for accessing, analyzing and exploring these data. The mission of CGD is to facilitate and accelerate research into Candida pathogenesis and biology, by curating the scientific literature in real time, and connecting literature-derived annotations to the latest version of the genomic sequence and its annotations...
October 13, 2016: Nucleic Acids Research
Gwennan André-Grégoire, Julie Gavard
Discovered decades ago, extracellular vesicles (EVs) emerge as dedicated organelles, able to deliver protected, specific cellular cues throughout the organism. While virtually every cell can release EVs, cancer cells co-opted this feature and efficiently unleashed them both in the tumor microenvironment and towards healthy tissues. This might contribute to tumor aggressiveness and spreading. Cancer-derived EVs that contain DNA, mRNA, miRNA, and packed and transmembrane proteins can operate locally or at distance...
October 13, 2016: Cell Adhesion & Migration
Ramon Gonzalez, Pilar Morales, Jordi Tronchoni, Gustavo Cordero-Bueso, Enrico Vaudano, Manuel Quirós, Maite Novo, Rafael Torres-Pérez, Eva Valero
Adaptation to changes in osmolarity is fundamental for the survival of living cells, and has implications in food and industrial biotechnology. It has been extensively studied in the yeast Saccharomyces cerevisiae, where the Hog1 stress activated protein kinase was discovered about 20 years ago. Hog1 is the core of the intracellular signaling pathway that governs the adaptive response to osmotic stress in this species. The main endpoint of this program is synthesis and intracellular retention of glycerol, as a compatible osmolyte...
2016: Frontiers in Microbiology
Geetanjali Chawla, Arthur Luhur, Nicholas Sokol
MicroRNAs are short noncoding, ~22-nucleotide RNAs that regulate protein abundance. The growth in our understanding of this class of RNAs has been rapid since their discovery just over a decade ago. We now appreciate that miRNAs are deeply embedded within the genetic networks that control basic features of metazoan cells including their identity, metabolism, and reproduction. The Drosophila melanogaster model system has made and will continue to make important contributions to this analysis. Intended as an introductory overview, here we review the current methods and resources available for functional analysis of fly miRNAs for those interested in performing this type of analysis...
2016: Methods in Molecular Biology
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