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A WW Domain-Containing Protein Forms Immune Nuclear Bodies against Begomoviruses

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molecular Plant 2018年第12期11卷 1449-1465页

作者： lara P. Calil lana P.S. Quadros Thais C. Araujo Christiane E.m. Duarte Bianca C. Gouveia-mageste Jose Cleydson F. Silva Otavio J.B. Brustolini Ruan m. Teixeira Caue N. Oliveira Rafael W.m.m. milagres Gilberto S. martins Joanne Chory Pedro A.B. Reis Joao Paulo B. machado Elizabeth P.B. Fontes Departament of Biochemistry and molecular Biology Universidade Federal de Vigosa Vigosa Minas Gerais 36570-000 Brazil Nati onal In stitute of Science and Tech no logy in Plant-Pest Interactions Bioagro Universidade Federal de Vicosa Vinosa Minas Gerais 36570-000 Brazil Departament of Genetics Universidade Federal do Rio de Janeiro Rio de Janeiro Rio de Janeiro Brazil Howard Hughes medical Institute and Plant Biology Laboratory The Salk Institute of Biological Studies La Jolla CA 92037 USA Agronomy Institute Universidade Federal de Vigosa Campus Florestal Florestal Minas Gerais 35690-000 Brazil These authors contributed equally to this article

The bipartite begomoviruses (Geminiviridae family), which are DNA viruses that replicate in the nucleus of infected cells, encode the nuclear shuttle protein (NSP) to facilitate the translocation of viral DNA from the nucleus to the cytoplasm via nuclear pores. This intracellular trafficking of NSP-DNA complexes is accessorized by the NSP-interacting guanosine triphosphatase (NIG) at the cytosolic side. Here, we report the nuclear redistribution of NIG by AtWWPI, a WW domain-containing protein that forms immune nuclear bodies (NBs) against begomoviruses. We demonstrated that AtWWPI relocates NIG from the cytoplasm to the nucleus where it is confined to AtWWP1-NBs, suggesting that the NIG-AtWWP1 interaction may interfere with the NIG pro-viral function associated with its cytosolic localization. Consistent with this assumpti on joss AtWWPI functi on cuased plants more susceptible to begomovirus infection, whereas overexpression of AWWP1 enhaneed plant resistance to begomovirus. Furthermore, we found that a mutant versi on of AtWWPI defective for NB formatio n was noIonger capable of interacti ng with and relocating NIG to the nucleus and lost its immune function against begomovirus. The antiviral function of AtWWP1-NBs, however, could be antagonized by viral infection that induced either the disruption or a decrease in the number of AtWWP1-NBs. Collectively, these results led us to propose that AtWWPI organizes nuclear structures into nuclear foci, which provide intrinsic immunity against begomovirus infection.

关键词： nuclear bodies antiviral immunity begomovirus NIG AtWWP1

nflammasomes in cancer： a double-edgecl sword

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Protein & Cell 2014年第1期5卷 12-20页

作者： Ryan Kolb Guang-Hui Liu Ann m. Janowski Fayyaz S. Sutterwala Weizhou Zhang Department of Pathology Carver College of Medicine University of Iowa Iowa City IA 52242 USA National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Graduate Program in Immunology Carver College Of Medicine University of Iowa iowa City IA 52242 USA Department of Internal medicine Carver College of Medicine University of Iowa Iowa City IA 52242 USA Veterans Affairs medical Center Iowa City IA 52241 USA

Chronic inflammatory responses have long been observed to be associated with various types of cancer and play decisive roles at different stages of cancer development. Inflammasomes, which are potent induc- ers of interleukin （IL）-I~ and IL-18 during infammation, are large protein complexes typically consisting of a Nod-like receptor （NLR）, the adapter protein ASC, and Caspase-1. During malignant transformation or cancer therapy, the inflammasomes are postulated to become activated in response to danger signals arising from the tumors or from therapy-induced damage to the tumor or healthy tissue. The activation of inflammasomes plays diverse and sometimes contrasting roles in cancer promotion and therapy depending on the specific con- text. Here we summarize the role of different inflamma- some complexes in cancer progression and therapy. Inflammasome components and pathways may provide novel targets to treat certain types of cancer; however, using such agents should be cautiously evaluated due to the complex roles that inflammasomes and pro- inflammatory cytokines play in immunity.

关键词： inflammasome cancer inflammation

Arabidopsis FtsZ2-1 and FtsZ2-2 Are Functionally Redundant, But FtsZ-Based Plastid Division Is Not Essential for Chloroplast Partitioning or Plant Growth and Development

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molecular Plant 2009年第6期2卷 1211-1222页

作者： Aaron J. Schmitz Jonathan m. Glynn Bradley J.S.C. Olson Kevin D. Stokes Katherine W. Osteryoung Department of Plant Biology 166 Plant Biology Bldg Michigan State University East Lansing MI 48824-1312 USA Cell and molecular Biology Program Michigan State University East Lansing MI 48824 USA Department of Energy-Plant Research Laboratory Michigan State University East Lansing MI 48824 USA Genetics Program Michigan State University East Lansing MI 48824 USA Biochemistry and molecular Biology Program Michigan State University East Lansing MI 48824 USA Present address: The salk Institute for Biological Studies Plant Molecular and Cellular Biology Laboratory La Jolla CA 92037 USA Present address: mycobacteria and Brucella Section NVSL/APHIS/USDA 1920 Dayton Ave Ames IA 50010 USA

FtsZ1 and FtsZ2 are phylogenetically distinct families of FtsZ in plants that co-localize to mid-plastid rings and facilitate division of chloroplasts. In plants, altered levels of either FtsZ1 or FtsZ2 cause dose-dependent defects in chloroplast division; thus, studies on the functional relationship between FtsZgenes require careful manipulation of FtsZ levels in vivo. To define the functional relationship between the two FtsZ2 genes in Arabidopsis thaliana, FtsZ2-1 and FtsZ2-2, we expressed FtsZ2-1 in an ftsZ2-2 null mutant, and vice versa, and determined whether the chloroplast division defects were rescued in plants expressing different total levels of FtsZ2. Full rescue was observed when either the FtsZ2-1 or FtsZ2-2 level approximated total FtsZ2 levels in wild-type （WT）. Additionally, FtsZ2-2 interacts with ARC6, as shown previously for FtsZ2- 1. These data indicate that FtsZ2-1 and FtsZ2-2 are functionally redundant for chloroplast division in Arabidopsis. To rigorously validate the requirement of each FtsZ family for chloroplast division, we replaced FtsZ1 with FtsZ2 in vivo, and vice versa, while maintaining the FtsZ level in the transgenic plants equal to that of the total level in WT. Chloroplast division defects were not rescued, demonstrating conclusively that FtsZ1 and FtsZ2 are non-redundant for maintenance of WT chloroplast numbers. Finally, we generated ftsZtriple null mutants and show that plants completely devoid of FtsZ protein are viable and fertile. As plastids are presumably essential organelles, these findings suggest that an FtsZ-independent mode of plastid partitioning may occur in higher plants.

关键词： Chloroplast plastid division FtsZ ARC6 PDV1.

Subcellular Redistribution of Root Aquaporins nduced by Hydrogen Peroxide

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molecular Plant 2015年第7期8卷 1103-1114页

作者： michael m. Wudick Xiaojuan Li Valeria Valentini Niko Geldner Joanne Chory Jinxing Lin Christophe maurel Doan-Trung Luu Biochimie et Physiologie moleculaire des Plantes Institut de Biologie Integrative des Plantes UMR 5004 CNRS/UMR 0386 INRA/Montpellier SupAgro/Universit~Montpellier 2 2 Place Viala F-34060 Montpellier Cedex 2 France Key Laboratory of Plant molecular Physiology Institute of Botany Chinese Academy of Sciences Beijing 100093 China Department of Plant molecular Biology Universite de Lausanne 1015 Lausanne Switzerland Plant molecular and Cellular Biology Laboratory The Salk Institute La Jolla CA 92037 USA Present address: Department of Cell Biology and molecular Genetics University of Maryland College Park MD 20742-5815 USA Present address: Instituto Gulbenkian de Ciencia 2780-156 Oeiras Portugal

Aquaporins are water channel proteins that mediate the fine-tuning of cell membrane water permeability during development or in response to environmental stresses. The present work focuses on the oxidative stress-induced redistribution of plasma membrane intrinsic protein （PIP） aquaporins from the plasma membrane （Pm） to intracellular membranes. This process was investigated in the Arabidopsis root. Su- crose density gradient centrifugation showed that exposure of roots to 0.5 mm H2O2 induces significant depletion in Pm fractions of several abundant PIP homologs after 15 rain. Analyses by single-particle tracking and fluorescence correlative spectroscopy showed that, in the Pm of epidermal cells, H2O2 treat- ment induces an increase in lateral motion and a reduction in the density of a fluorescently tagged form of the prototypal AtPIP2;1 isoform, respectively. Co-expression analyses of AtPIP2;1 with endomembrane markers revealed that H2O2 triggers AtPIP2;1 accumulation in the late endosomal compartments. Life- time analyses established that the high stability of PIPs was maintained under oxidative stress conditions, suggesting that H2O2 triggers a mechanism for intracellular sequestration of Pm aquaporins without further degradation. In addition to information on cellular regulation of aquaporins, this study provides novel and complementary insights into the dynamic remodeling of plant internal membranes during oxida- tive stress responses.

关键词： Arabidopsis aquaporin stress reactive oxygen species root

NCoR1 protects positive-selecting thymocytes from negative selection

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NCoR1 protects positive-selecting thymocytes from negative s...

Gatekeepers of The Guardian:Insights Into p53 Activation by mDm2 and mDm4 Revealed by mouse models and In Vitro Studies

第9届中国中西医结合学会妇产科专业委员会第二次学术会议

作者： Na Zhang Jianrong Wang Nanhai He Ronald m.Evans Dajin Li Ling Wang Qibin Leng Laboratory for Reproductive Immunology Hospital & Institute of Obstetrics and Gynecology IBS Fudan University Shanghai Medical College The Academy of Integrative medicine of Fudan University Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Key Laboratory of molecular Virology and Immunology Institut Pasteur of Shanghai Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Gene Expression Laboratory Salk Institute for Biological Studies

机体自身的免疫调控、炎症反应以及抵抗外来感染的过程中,T细胞发挥着不可或缺的作用。在胸腺发育中,T细胞受体信号介导阳性选择和阴性选择,在这个过程中需要精密的转录调控以开启和关闭细胞的增殖与凋亡通道。之前研究表明,转录辅抑制...

机体自身的免疫调控、炎症反应以及抵抗外来感染的过程中,T细胞发挥着不可或缺的作用。在胸腺发育中,T细胞受体信号介导阳性选择和阴性选择,在这个过程中需要精密的转录调控以开启和关闭细胞的增殖与凋亡通道。之前研究表明,转录辅抑制子NCoR1很可能在T细胞胸腺发育中发挥重要作用。我们建立了T细胞特异性缺失NCoR的小鼠品系,发现与全身性NCoR1缺失小鼠胚胎胸腺

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Gatekeepers of The Guardian:Insights Into p53 Activation by ...

mutations in foregut SOX2^+ cells induce efficient proliferation via CXCR2 pathway

第四届中国肿瘤学术大会暨第五届海峡两岸肿瘤学术会议

作者： Geoffrey m. Wahl Kurt Krummel Crystal Lee Chung-Wen Liu Luo-Wei Rodewald Franck Toledo mark Wade Ee-Tsin Wong The salk Institute for Biological Studies The salk Institute for Biological Studies The salk Institute for Biological Studies The salk Institute for Biological Studies and Institut Pasteur Unité d’Expression Génétique et maladies The salk Institute for Biological Studies The salk Institute for Biological Studies

＜正＞Background: The p53 tumor suppressor has been called the "Guardian of the Genome" since it prevents cells that have irrepairable DNA damage from proliferating. p53 is a stress responsive transcriptional regulator that is activated by many adverse conditions that impinge on developing tumor cells to prevent them from dividing. This ensures genetic stability, and prevents the emergence of genetically variant clones. Conversely, loss of p53 allows cells to proliferate under challenging, potentially genotoxic conditions. Thus, loss of p53 function is highly selected during tumor progres-

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Protein & Cell 2019年第7期10卷 485-495页

作者： Tomoaki Hishida Eric Vazquez-Ferrer Yuriko Hishida-Nozaki Ignacio Sancho-martinez Yuta Takahashi Fumiyuki Hatanaka Jun Wu Alejandro Ocampo Pradeep Reddy min-Zu Wu Laurie Gerken Reuben J. Shaw Concepcion Rodriguez Esteban Christopher Benner Hiroshi Nakagawa Pedro Guillen Garcia Estrella Nunez Delicado Antoni Castells Josep m. Campistol Guang-Hui Liu Juan Carlos Izpisua Belmonte Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Advaneed Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric Disorders Xuanwu Hospital Capital Medical University Beijing 100053 China National Laboratory of Biomacromolecules CAS Center for Excellence in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China University of the Chinese Academy of Sciences Beijing 100049 China Insitute for Stem Cell and Regeneration Chinese Academy of Sciences Beijing 100101 China Beijing Institute for Brain Disorder Beijing 100069 China Universidad Catolica San Antonio de Murcia Campus de los Jeronimos 135 Guadalupe 30107 Spain molecular and Cell Biology Laboratory Dulbecco Center for Cancer Research Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Howard Hughes medical Institute Dulbecco Center for Cancer Research Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Integrative Genomics Core Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Division of Gastroenterology Department of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104 USA Abramson Cancer Center University of Pennsylvania Philadelphia PA 19104 USA Department of Traumatology and Research Unit Clinica CEMTRO Av. Ventisquero de la Condesa 42 Madrid 28035 Spain Gastroenterology Department Hospital Clinic University of Barcelona IDIBAPS CIBEREHD Barcelona 08036 Spain

Identification of the precise molecular pathways involved in oncogene-induced transformation may help us gain a better understanding of tumor initiation and promotion. Here, we demonstrate that SOX2^+ foregut epithelial cells are prone to oncogenic transformation upon mutagenic insults, such as Kras^G12D and p53 deletion. GFP-based lineage-tracing experiments indicate that SOX2^+ cells are the cells-of-origin of esophagus and stomach hyperplasia. Our observations indicate distinct roles for oncogenic KRAS mutation and P53 deletion. p53 homozygous deletion is required for the acquisition of an invasive potential, and Kras^G12D expression, but not p53 deletion, suffices for tumor formation. Global gene expression analysis reveals secreting factors upregulated in the hyperplasia induced by oncogenic KRAS and highlights a crucial role for the CXCR2 pathway in driving hyperplasia. Collectively, the array of genetic models presented here demonstrate that stratified epithelial cells are susceptible to oncogenic insults, which may lead to a better understanding of tumor initiation and aid in the design of new cancer therapeutics.

关键词： Sox2 tumor CXCR2 stratified epithelia

Fatty acid desaturation by stearoyl-CoA desaturase-1 controls regulatory T cell differentiation and autoimmunity

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Cellular & molecular Immunology 2023年第6期20卷 666-679页

作者： Elien Grajchen melanie Loix Paulien Baeten Beatriz F.Côrte-Real Ibrahim Hamad Sam Vanherle mansour Haidar Jonas Dehairs Jelle Y.Broos James m.Ntambi Robert Zimmermann Rolf Breinbauer Piet Stinissen Niels Hellings Sanne G.S.Verberk Gijs Kooij martin Giera Johannes V.Swinnen Bieke Broux markus Kleinewietfeld Jerome J.A.Hendriks Jeroen F.J.Bogie Department of Immunology and Infection Biomedical Research InstituteHasselt UniversityDiepenbeekBelgium University mS Center Hasselt PeltBelgium Neuro-Immune Connections and Repair Lab Department of Immunology and InfectionBiomedical Research InstituteHasselt UniversityDiepenbeekBelgium VIB Laboratory of Translational Immunomodulation VIB Center for Inflammation ResearchHasselt UniversityDiepenbeekBelgium Department of Oncology Laboratory of Lipid Metabolism and CancerLKI–Leuven Cancer InstituteKU Leuven-University of LeuvenLeuvenBelgium Department of molecular Cell Biology and Immunology Amsterdam University Medical CenterVrije Universiteit AmsterdamAmsterdam NeuroscienceMS Center AmsterdamAmsterdamThe Netherlands Center for Proteomics and metabolomics Leiden University Medical CenterLeidenThe Netherlands Department of Biochemistry Department of Nutritional SciencesUniversity of Wisconsin-MadisonMadisonUSA Institute of molecular Biosciences University of GrazGrazAustria BioTechmed-Graz GrazAustria Institute of Organic Chemistry Graz University of TechnologyGrazAustria Cardiovascular Research Institute maastricht Department of Internal MedicineMaastricht UniversityMaastrichtThe Netherlands

The imbalance between pathogenic and protective T cell subsets is a cardinal feature of autoimmune disorders such as multiple sclerosis(mS).Emerging evidence indicates that endogenous and dietary-induced changes in fatty acid metabolism have a major impact on both T cell fate and *** date,however,the molecular mechanisms that underlie the impact of fatty acid metabolism on T cell physiology and autoimmunity remain poorly ***,we report that stearoyl-CoA desaturase-1(SCD1),an enzyme essential for the desaturation of fatty acids and highly regulated by dietary factors,acts as an endogenous brake on regulatory T-cell(Treg)differentiation and augments autoimmunity in an animal model of mS in a T cell-dependent *** by RNA sequencing and lipidomics analysis,we found that the absence of Scd1 in T cells promotes the hydrolysis of triglycerides and phosphatidylcholine through adipose triglyceride lipase(ATGL).ATGL-dependent release of docosahexaenoic acid enhanced Treg differentiation by activating the nuclear receptor peroxisome proliferator-activated receptor *** findings identify fatty acid desaturation by SCD1 as an essential determinant of Treg differentiation and autoimmunity,with potentially broad implications for the development of novel therapeutic strategies and dietary interventions for autoimmune disorders such as mS.

关键词： Regulatory T cells Autoimmunity Fatty acid metabolism Stearoyl-CoA desaturase-1 multiple sclerosis

Temperature changes in the root ecosystem affect plant functionality

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Plant Communications 2023年第3期4卷 197-214页

作者： mary Paz González-García Carlos m.Conesa Alberto Lozano-Enguita Victoria Baca-González Bárbara Simancas Sara Navarro-Neila maría Sánchez-Bermúdez Isai Salas-González Elena Caro Gabriel Castrillo Juan C.del Pozo Centro de Biotecnología y Genómica de Plantas(UPm-INIA/CSIC) Universidad Politécnica de Madrid(UPM)-Instituto Nacional de Investigación y Tecnología Agrariay Alimentaria-CSIC(INIA/CSIC)Campus Montegancedo28223 Pozuelo de Alarcón(Madrid)Spain Departamento de Biotecnología-Biología Vegetal Escuela Técnica Superior de Ingeniería AgronómicaAlimentaria y de BiosistemasUniversidad Politécnica de Madrid(UPM)28040 MadridSpain Undergraduate Program in Genomic Sciences Center for Genomics SciencesUniversidad Nacional Autonóma de MéxicoAv.Universidad s/n.Col.ChamilpaCuernavaca 62210MorelosMéxico Future Food Beacon of Excellence&School of Biosciences University of NottinghamSutton BoningtonUK

Climate change is increasing the frequency of extreme heat events that aggravate its negative impact on plant development and agricultural *** experiments designed to study plant adaption to heat stress apply homogeneous high temperatures to both shoot and ***,this treatment does not mimic the conditions in natural fields,where roots grow in a dark environment with a descending temperature *** high temperatures severely decrease cell division in the root meristem,compromising root growth,while increasing the division of quiescent center cells,likely in an attempt to maintain the stem cell niche under such harsh ***,we engineered the TGRooZ,a device that generates a temperature gradient for in vitro or greenhouse growth *** root systems of plants exposed to high shoot temperatures but cultivated in theTGRooZ grow efficiently and maintain their functionality to sustain proper shoot growth and ***,gene expression and rhizosphere or root microbiomecomposition are significantly less affected in TGRooZ-grown roots than in high-temperature-grown roots,correlating with higher root *** data indicate that use of the TGRooZ in heat-stress studies can improve our knowledge of plant response to high temperatures,demonstrating its applicability from laboratory studies to the field.

关键词： heat stress root temperature gradient nutrition gene expression microbiome