Functional dissection of an innate immune response by a genome-wide RNAi screen.

Abstract:

:The innate immune system is ancient and highly conserved. It is the first line of defense and the only recognizable immune system in the vast majority of metazoans. Signaling events that convert pathogen detection into a defense response are central to innate immunity. Drosophila has emerged as an invaluable model organism for studying this regulation. Activation of the NF-kappaB family member Relish by the caspase-8 homolog Dredd is a central, but still poorly understood, signaling module in the response to gram-negative bacteria. To identify the genes contributing to this regulation, we produced double-stranded RNAs corresponding to the conserved genes in the Drosophila genome and used this resource in genome-wide RNA interference screens. We identified numerous inhibitors and activators of immune reporters in a cell culture model. Epistatic interactions and phenotypes defined a hierarchy of gene action and demonstrated that the conserved gene sickie is required for activation of Relish. We also showed that a second gene, defense repressor 1, encodes a product with characteristics of an inhibitor of apoptosis protein that inhibits the Dredd caspase to maintain quiescence of the signaling pathway. Molecular analysis revealed that Defense repressor 1 is upregulated by Dredd in a feedback loop. We propose that interruption of this feedback loop contributes to signal transduction.

journal_name

PLoS Biol

journal_title

PLoS biology

authors

Foley E,O'Farrell PH

doi

10.1371/journal.pbio.0020203

keywords:

subject

Has Abstract

pub_date

2004-08-01 00:00:00

pages

E203

issue

8

eissn

1544-9173

issn

1545-7885

journal_volume

2

pub_type

杂志文章
  • Identification of FAM173B as a protein methyltransferase promoting chronic pain.

    abstract::Chronic pain is a debilitating problem, and insights in the neurobiology of chronic pain are needed for the development of novel pain therapies. A genome-wide association study implicated the 5p15.2 region in chronic widespread pain. This region includes the coding region for FAM173B, a functionally uncharacterized pr...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.2003452

    authors: Willemen HLDM,Kavelaars A,Prado J,Maas M,Versteeg S,Nellissen LJJ,Tromp J,Gonzalez Cano R,Zhou W,Jakobsson ME,Małecki J,Posthuma G,Habib AM,Heijnen CJ,Falnes PØ,Eijkelkamp N

    更新日期:2018-02-14 00:00:00

  • The DEAH-box helicase Dhr1 dissociates U3 from the pre-rRNA to promote formation of the central pseudoknot.

    abstract::In eukaryotes, the highly conserved U3 small nucleolar RNA (snoRNA) base-pairs to multiple sites in the pre-ribosomal RNA (pre-rRNA) to promote early cleavage and folding events. Binding of the U3 box A region to the pre-rRNA is mutually exclusive with folding of the central pseudoknot (CPK), a universally conserved r...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1002083

    authors: Sardana R,Liu X,Granneman S,Zhu J,Gill M,Papoulas O,Marcotte EM,Tollervey D,Correll CC,Johnson AW

    更新日期:2015-02-24 00:00:00

  • The cutaneous rabbit illusion affects human primary sensory cortex somatotopically.

    abstract::We used functional magnetic resonance imaging (fMRI) to study neural correlates of a robust somatosensory illusion that can dissociate tactile perception from physical stimulation. Repeated rapid stimulation at the wrist, then near the elbow, can create the illusion of touches at intervening locations along the arm, a...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0040069

    authors: Blankenburg F,Ruff CC,Deichmann R,Rees G,Driver J

    更新日期:2006-03-01 00:00:00

  • Cell-by-cell dissection of gene expression and chromosomal interactions reveals consequences of nuclear reorganization.

    abstract::The functional consequences of long-range nuclear reorganization were studied in a cell-by-cell analysis of gene expression and long-range chromosomal interactions in the Drosophila eye and eye imaginal disk. Position-effect variegation was used to stochastically perturb gene expression and probe nuclear reorganizatio...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0030067

    authors: Harmon B,Sedat J

    更新日期:2005-03-01 00:00:00

  • Science incubators: synthesis centers and their role in the research ecosystem.

    abstract::How should funding agencies enable researchers to explore high-risk but potentially high-reward science? One model that appears to work is the NSF-funded synthesis center, an incubator for community-led, innovative science. ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001468

    authors: Rodrigo A,Alberts S,Cranston K,Kingsolver J,Lapp H,McClain C,Smith R,Vision T,Weintraub J,Wiegmann B

    更新日期:2013-01-01 00:00:00

  • Alerting or Somnogenic Light: Pick Your Color.

    abstract::In mammals, light exerts pervasive effects on physiology and behavior in two ways: indirectly through clock synchronization and the phase adjustment of circadian rhythms, and directly through the promotion of alertness and sleep, respectively, in diurnal and nocturnal species. A recent report by Pilorz and colleagues ...

    journal_title:PLoS biology

    pub_type: 评论,杂志文章

    doi:10.1371/journal.pbio.2000111

    authors: Bourgin P,Hubbard J

    更新日期:2016-08-15 00:00:00

  • Control of apoptosis by asymmetric cell division.

    abstract::Asymmetric cell division and apoptosis (programmed cell death) are two fundamental processes that are important for the development and function of multicellular organisms. We have found that the processes of asymmetric cell division and apoptosis can be functionally linked. Specifically, we show that asymmetric cell ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0060084

    authors: Hatzold J,Conradt B

    更新日期:2008-04-08 00:00:00

  • Cryptochrome mediates light-dependent magnetosensitivity of Drosophila's circadian clock.

    abstract::Since 1960, magnetic fields have been discussed as Zeitgebers for circadian clocks, but the mechanism by which clocks perceive and process magnetic information has remained unknown. Recently, the radical-pair model involving light-activated photoreceptors as magnetic field sensors has gained considerable support, and ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1000086

    authors: Yoshii T,Ahmad M,Helfrich-Förster C

    更新日期:2009-04-07 00:00:00

  • PiVR: An affordable and versatile closed-loop platform to study unrestrained sensorimotor behavior.

    abstract::Tools enabling closed-loop experiments are crucial to delineate causal relationships between the activity of genetically labeled neurons and specific behaviors. We developed the Raspberry Pi Virtual Reality (PiVR) system to conduct closed-loop optogenetic stimulation of neural functions in unrestrained animals. PiVR i...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000712

    authors: Tadres D,Louis M

    更新日期:2020-07-14 00:00:00

  • Flight speeds among bird species: allometric and phylogenetic effects.

    abstract::Flight speed is expected to increase with mass and wing loading among flying animals and aircraft for fundamental aerodynamic reasons. Assuming geometrical and dynamical similarity, cruising flight speed is predicted to vary as (body mass)(1/6) and (wing loading)(1/2) among bird species. To test these scaling rules an...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0050197

    authors: Alerstam T,Rosén M,Bäckman J,Ericson PG,Hellgren O

    更新日期:2007-08-01 00:00:00

  • GPCRs show widespread differential mRNA expression and frequent mutation and copy number variation in solid tumors.

    abstract::G protein-coupled receptors (GPCRs) are the most widely targeted gene family for Food and Drug Administration (FDA)-approved drugs. To assess possible roles for GPCRs in cancer, we analyzed The Cancer Genome Atlas (TCGA) data for mRNA expression, mutations, and copy number variation (CNV) in 20 categories and 45 subty...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000434

    authors: Sriram K,Moyung K,Corriden R,Carter H,Insel PA

    更新日期:2019-11-25 00:00:00

  • BEAF regulates cell-cycle genes through the controlled deposition of H3K9 methylation marks into its conserved dual-core binding sites.

    abstract::Chromatin insulators/boundary elements share the ability to insulate a transgene from its chromosomal context by blocking promiscuous enhancer-promoter interactions and heterochromatin spreading. Several insulating factors target different DNA consensus sequences, defining distinct subfamilies of insulators. Whether e...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0060327

    authors: Emberly E,Blattes R,Schuettengruber B,Hennion M,Jiang N,Hart CM,Käs E,Cuvier O

    更新日期:2008-12-23 00:00:00

  • Anything you can do, you can do better: neural substrates of incentive-based performance enhancement.

    abstract::Performance-based pay schemes in many organizations share the fundamental assumption that the performance level for a given task will increase as a function of the amount of incentive provided. Consistent with this notion, psychological studies have demonstrated that expectations of reward can improve performance on a...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001272

    authors: Liljeholm M,O'Doherty JP

    更新日期:2012-02-01 00:00:00

  • A non-natural nucleotide uses a specific pocket to selectively inhibit telomerase activity.

    abstract::Telomerase, a unique reverse transcriptase that specifically extends the ends of linear chromosomes, is up-regulated in the vast majority of cancer cells. Here, we show that an indole nucleotide analog, 5-methylcarboxyl-indolyl-2'-deoxyriboside 5'-triphosphate (5-MeCITP), functions as an inhibitor of telomerase activi...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000204

    authors: Hernandez-Sanchez W,Huang W,Plucinsky B,Garcia-Vazquez N,Robinson NJ,Schiemann WP,Berdis AJ,Skordalakes E,Taylor DJ

    更新日期:2019-04-05 00:00:00

  • Laws of concatenated perception: Vision goes for novelty, decisions for perseverance.

    abstract::Every instant of perception depends on a cascade of brain processes calibrated to the history of sensory and decisional events. In the present work, we show that human visual perception is constantly shaped by two contrasting forces exerted by sensory adaptation and past decisions. In a series of experiments, we used ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000144

    authors: Pascucci D,Mancuso G,Santandrea E,Della Libera C,Plomp G,Chelazzi L

    更新日期:2019-03-05 00:00:00

  • Inhibitor of the tyrosine phosphatase STEP reverses cognitive deficits in a mouse model of Alzheimer's disease.

    abstract::STEP (STriatal-Enriched protein tyrosine Phosphatase) is a neuron-specific phosphatase that regulates N-methyl-D-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking, as well as ERK1/2, p38, Fyn, and Pyk2 activity. STEP is overactive in several neuropsychiatr...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001923

    authors: Xu J,Chatterjee M,Baguley TD,Brouillette J,Kurup P,Ghosh D,Kanyo J,Zhang Y,Seyb K,Ononenyi C,Foscue E,Anderson GM,Gresack J,Cuny GD,Glicksman MA,Greengard P,Lam TT,Tautz L,Nairn AC,Ellman JA,Lombroso PJ

    更新日期:2014-08-05 00:00:00

  • A Src-like inactive conformation in the abl tyrosine kinase domain.

    abstract::The improper activation of the Abl tyrosine kinase results in chronic myeloid leukemia (CML). The recognition of an inactive conformation of Abl, in which a catalytically important Asp-Phe-Gly (DFG) motif is flipped by approximately 180 degrees with respect to the active conformation, underlies the specificity of the ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0040144

    authors: Levinson NM,Kuchment O,Shen K,Young MA,Koldobskiy M,Karplus M,Cole PA,Kuriyan J

    更新日期:2006-05-01 00:00:00

  • Ligands for pheromone-sensing neurons are not conformationally activated odorant binding proteins.

    abstract::Pheromones form an essential chemical language of intraspecific communication in many animals. How olfactory systems recognize pheromonal signals with both sensitivity and specificity is not well understood. An important in vivo paradigm for this process is the detection mechanism of the sex pheromone (Z)-11-octadecen...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001546

    authors: Gomez-Diaz C,Reina JH,Cambillau C,Benton R

    更新日期:2013-01-01 00:00:00

  • A Cullin1-based SCF E3 ubiquitin ligase targets the InR/PI3K/TOR pathway to regulate neuronal pruning.

    abstract::Pruning that selectively eliminates unnecessary axons/dendrites is crucial for sculpting the nervous system during development. During Drosophila metamorphosis, dendrite arborization neurons, ddaCs, selectively prune their larval dendrites in response to the steroid hormone ecdysone, whereas mushroom body γ neurons sp...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001657

    authors: Wong JJ,Li S,Lim EK,Wang Y,Wang C,Zhang H,Kirilly D,Wu C,Liou YC,Wang H,Yu F

    更新日期:2013-09-01 00:00:00

  • Primary visual cortex activity along the apparent-motion trace reflects illusory perception.

    abstract::The illusion of apparent motion can be induced when visual stimuli are successively presented at different locations. It has been shown in previous studies that motion-sensitive regions in extrastriate cortex are relevant for the processing of apparent motion, but it is unclear whether primary visual cortex (V1) is al...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0030265

    authors: Muckli L,Kohler A,Kriegeskorte N,Singer W

    更新日期:2005-08-01 00:00:00

  • Host-parasite interactions and the evolution of gene expression.

    abstract::Interactions between hosts and parasites provide an ongoing source of selection that promotes the evolution of a variety of features in the interacting species. Here, we use a genetically explicit mathematical model to explore how patterns of gene expression evolve at genetic loci responsible for host resistance and p...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0030203

    authors: Nuismer SL,Otto SP

    更新日期:2005-07-01 00:00:00

  • The COVID-19 response illustrates that traditional academic reward structures and metrics do not reflect crucial contributions to modern science.

    abstract::The COVID-19 pandemic has motivated many open and collaborative analytical research projects with real-world impact. However, despite their value, such activities are generally overlooked by traditional academic metrics. Science is ultimately improved by analytical work, whether ensuring reproducible and well-document...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000913

    authors: Kucharski AJ,Funk S,Eggo RM

    更新日期:2020-10-16 00:00:00

  • Sex chromosomes control vertical transmission of feminizing Wolbachia symbionts in an isopod.

    abstract::Microbial endosymbiosis is widespread in animals, with major ecological and evolutionary implications. Successful symbiosis relies on efficient vertical transmission through host generations. However, when symbionts negatively affect host fitness, hosts are expected to evolve suppression of symbiont effects or transmi...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000438

    authors: Becking T,Chebbi MA,Giraud I,Moumen B,Laverré T,Caubet Y,Peccoud J,Gilbert C,Cordaux R

    更新日期:2019-10-10 00:00:00

  • A role for myosin VI in the localization of axonal proteins.

    abstract::In neurons polarized trafficking of vesicle-bound membrane proteins gives rise to the distinct molecular composition and functional properties of axons and dendrites. Despite their central role in shaping neuronal form and function, surprisingly little is known about the molecular processes that mediate polarized targ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001021

    authors: Lewis TL Jr,Mao T,Arnold DB

    更新日期:2011-03-01 00:00:00

  • Correction: Tracking Resilience to Infections by Mapping Disease Space.

    abstract::[This corrects the article DOI: 10.1371/journal.pbio.1002436.]. ...

    journal_title:PLoS biology

    pub_type: 已发布勘误

    doi:10.1371/journal.pbio.1002494

    authors: PLOS Biology Staff.

    更新日期:2016-06-08 00:00:00

  • Some agreement on kin selection and eusociality?

    abstract::The authors of "Relatedness, Conflict, and the Evolution of Eusociality" respond to objections raised by Martin Nowak and Benjamin Allen. ...

    journal_title:PLoS biology

    pub_type: 评论,杂志文章

    doi:10.1371/journal.pbio.1002133

    authors: Queller DC,Rong S,Liao X

    更新日期:2015-04-24 00:00:00

  • Developing international open science collaborations: Funder reflections on the Open Science Prize.

    abstract::The Open Science Prize was established with the following objectives: first, to encourage the crowdsourcing of open data to make breakthroughs that are of biomedical significance; second, to illustrate that funders can indeed work together when scientific interests are aligned; and finally, to encourage international ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.2002617

    authors: Kittrie E,Atienza AA,Kiley R,Carr D,MacFarlane A,Pai V,Couch J,Bajkowski J,Bonner JF,Mietchen D,Bourne PE

    更新日期:2017-08-01 00:00:00

  • Facilitation of task performance and removal of the effects of sleep deprivation by an ampakine (CX717) in nonhuman primates.

    abstract::The deleterious effects of prolonged sleep deprivation on behavior and cognition are a concern in modern society. Persons at risk for impaired performance and health-related issues resulting from prolonged sleep loss would benefit from agents capable of reducing these detrimental effects at the time they are sleep dep...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0030299

    authors: Porrino LJ,Daunais JB,Rogers GA,Hampson RE,Deadwyler SA

    更新日期:2005-09-01 00:00:00

  • Quantifying the effects of temperature on mosquito and parasite traits that determine the transmission potential of human malaria.

    abstract::Malaria transmission is known to be strongly impacted by temperature. The current understanding of how temperature affects mosquito and parasite life history traits derives from a limited number of empirical studies. These studies, some dating back to the early part of last century, are often poorly controlled, have l...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.2003489

    authors: Shapiro LLM,Whitehead SA,Thomas MB

    更新日期:2017-10-16 00:00:00

  • Low-level toxicity of chemicals: No acceptable levels?

    abstract::Over the past 3 decades, in a series of studies on some of the most extensively studied toxic chemicals and pollutants, scientists have found that the amount of toxic chemical linked with the development of a disease or death-which is central to determining "safe" or "hazardous" levels-is proportionately greater at th...

    journal_title:PLoS biology

    pub_type: 社论

    doi:10.1371/journal.pbio.2003066

    authors: Lanphear BP

    更新日期:2017-12-19 00:00:00