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  • Cell Research
    macroautophagy regulation in mammalian cells Maryam Mehrpour 1 2 Audrey Esclatine 1 2 Isabelle Beau 1 2 and Patrice Codogno 1 2 1 INSERM U756 2 Universit Paris Sud 11 Facult de Pharmacie 5 rue Jean Baptiste Cl閙ent 92290 Ch鈚enay Malabry France Correspondence Patrice Codogno Tel 33146835720 E mail patrice codogno u psud fr Macroautophagy is a multistep vacuolar degradation pathway terminating in the lysosomal compartment and it is of fundamental importance in tissue homeostasis In this review we consider macroautophagy in the light of recent advances in our understanding of the formation of autophagosomes which are double membrane bound vacuoles that sequester cytoplasmic cargos and deliver them to lysosomes In most cases this final step is preceded by a maturation step during which autophagosomes interact with the endocytic pathway The discovery of AuTophaGy related genes has greatly increased our knowledge about the mechanism responsible for autophagosome formation and there has also been progress in the understanding of molecular aspects of autophagosome maturation Finally the regulation of autophagy is now better understood because of the discovery that the activity of Atg complexes is targeted by protein kinases and owing to the importance of nuclear regulation via transcription factors in regulating

    Original URL path: http://www.cell-research.com/arts.asp?id=500 (2016-02-14)
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  • Cell Research
    Charles Street Baltimore MD 21218 2685 USA 2 Laboratory of Molecular Immunology National Heart Lung and Blood Institute National Institutes of Health Bethesda MD 20892 USA Correspondence Xin Chen Tel 1 410 516 4576 E mail xchen32 jhu edu Both transcription and post transcriptional processes such as alternative splicing play crucial roles in controlling developmental programs in metazoans Recently emerged RNA seq method has brought our understanding of eukaryotic transcriptomes to a new level because it can resolve both gene expression level and alternative splicing events simultaneously To gain a better understanding of cellular differentiation in gonads we analyzed mRNA profiles from Drosophila testes and ovaries using RNA seq We identified a set of genes that have sex specific isoforms in wild type WT gonads including several transcription factors We found that differentiation of sperms from undifferentiated germ cells induced a dramatic downregulation of RNA splicing factors Our data confirmed that RNA splicing events are significantly more frequent in the undifferentiated cell enriched bag of marbles bam mutant testis but downregulated upon differentiation in WT testis Consistent with this we showed that genes required for meiosis and terminal differentiation in WT testis were mainly regulated at the transcriptional level but not by alternative splicing Unexpectedly we observed an increase in expression of all families of chromatin remodeling factors and histone modifying enzymes in the undifferentiated cell enriched bam testis More interestingly chromatin regulators and histone modifying enzymes with opposite enzymatic activities are coenriched in undifferentiated cells in testis suggesting that these cells may possess dynamic chromatin architecture Finally our data revealed many new features of the Drosophila gonadal transcriptomes and will lead to a more comprehensive understanding of how differential gene expression and splicing regulate gametogenesis in Drosophila Our data provided a foundation for the systematic study of gene expression

    Original URL path: http://www.cell-research.com/arts.asp?id=501 (2016-02-14)
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  • Cell Research
    Liu 1 Yuehai Ke 1 Jianmin Si 3 and Tianhua Zhou 1 1 The Center for Diseases Modeling and Program in Molecular and Cell Biology Zhejiang University School of Medicine Hangzhou 310058 China 2 Zhejiang University School of Medicine Hangzhou 310058 China 3 Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou 310016 China Correspondence Jianmin Si Tianhua Zhou Tel 86 571 8600 6788 86 571 8820 8258 E mail jianmin si zju edu cn tzhou zju edu cn Emerging evidence has shown the association of aberrantly expressed microRNAs miRNAs with tumor development and progression However little is known about the potential role of miRNAs in gastric carcinogenesis Here we performed miRNA microarray to screen miRNAs differentially expressed in the paired gastric cancer and their adjacent nontumor tissues and found that miR 375 was greatly downregulated in gastric cancer tissues Quantitative real time PCR analysis verified that miR 375 expression was significantly decreased in more than 90 of primary gastric cancers compared with their nontumor counterparts from patients undergoing gastric resection Overexpression of miR 375 significantly inhibited gastric cancer cell proliferation in vitro and in vivo Forced expression of miR 375 in gastric cancer cells significantly reduced the protein level of Janus kinase 2 JAK2 and repressed the activity of a luciferase reporter carrying the 3 untranslated region of JAK2 which was abolished by mutation of the predicted miR 375 binding site indicating that JAK2 may be a miR 375 target gene Either inhibition of JAK2 activity by AG490 or silencing of JAK2 by RNAi suppressed gastric cancer cell proliferation resembling that of miR 375 overexpression Moreover ectopic expression of JAK2 can partially reverse the inhibition of cell proliferation caused by miR 375 Finally we found a significant inverse correlation between miR 375 expression and JAK2 protein level

    Original URL path: http://www.cell-research.com/arts.asp?id=502 (2016-02-14)
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  • Cell Research
    Molecular Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences 310 Yueyang Road Shanghai 100031 China 2 Shanghai Key laboratory of Molecular Andrology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences 310 Yueyang Road Shanghai 100031 China 3 Affiliated Hospital of Nantong University Nantong 226001 China 4 Laboratory of Molecular Cell Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences 310 Yueyang Road Shanghai 100031 China Correspondence Pin Adele Chen Charlie Degui Chen E mail pinchen sibs ac cn cdchen sibs ac cn Dimethylation of histone H3 lysine 9 H3K9me2 is an important epigenetic mark associated with transcription repression Here we identified PHF8 a JmjC domain containing protein as a histone demethylase specific for this repressing mark Recombinant full length wild type protein could remove methylation from H3K9me2 but mutation of a conserved histidine to alanine H247A abolished the demethylase activity Overexpressed exogenous PHF8 was colocalized with B23 staining Endogenous PHF8 was also colocalized with B23 and fibrillarin two well established nucleolus proteins suggesting that PHF8 is localized in the nucleolus and may regulate rRNA transcription Indeed PHF8 bound

    Original URL path: http://www.cell-research.com/arts.asp?id=503 (2016-02-14)
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  • Cell Research
    The ubiquitin specific protease 17 is involved in virus triggered type I IFN signaling Rui Chen Lu Zhang Bo Zhong Bo Tan Yu Liu and Hong Bing Shu College of Life Sciences Wuhan University Wuhan 430072 China Correspondence Hong Bing Shu Tel 86 27 68753795 E mail shuh whu edu cn Viral infection initiates a series of signaling cascades that activate the transcription factors nuclear factor kappa B and interferon regulatory factor 3 which collaborate to induce transcription of genes for type I interferons IFNs and other cytokines Here we report that the deubiquitinating enzyme ubiquitin specific protease 17 USP17 is required for virus induced RIG I and melanoma differentiation associated protein 5 MDA5 mediated type I IFN signaling Knockdown of endogenous USP17 inhibited virus cytoplasmic poly I C and poly dA dT induced activation of the IFN β promoter and cellular antiviral responses We further found that knockdown of USP17 inhibited RIG I and MDA5 induced but not downstream activator induced activation of the IFN β promoter which was correlated with an increase in ubiquitination levels of RIG I and MDA5 Taken together our findings suggest that USP17 functions through deubiquitination of RIG I and MDA5 to regulate virus

    Original URL path: http://www.cell-research.com/arts.asp?id=504 (2016-02-14)
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  • Cell Research
    Mihai Cikala 1 Beate Stiening 1 Tina Käsbauer 1 Gerhardt Zenner 1 Tanja Popp 1 Anita Wagner 1 Regina T Knapp 1 Andreas H Huber 1 Michaela Grunert 1 Johannes Söding 2 Charles N David 1 and Angelika Böttger 1 1 Department Biology II Ludwig Maximilians University M黱chen Gro遠aderner Str 2 82152 Planegg Martinsried Germany 2 Gene Centre Feodor Lynen Str 25 81377 M黱chen Germany Correspondence Angelika Böttger Tel 0049 0 89 218074 279 E mail boettger zi biologie uni muenchen de The fresh water polyp Hydra belongs to the phylum Cnidaria which diverged from the metazoan lineage before the appearance of bilaterians In order to understand the evolution of apoptosis in metazoans we have begun to elucidate the molecular cell death machinery in this model organism Based on ESTs and the whole Hydra genome assembly we have identified 15 caspases We show that one is activated during apoptosis four have characteristics of initiator caspases with N terminal DED CARD or DD domain and two undergo autoprocessing in vitro In addition we describe seven Bcl 2 like and two Bak like proteins For most of the Bcl 2 family proteins we have observed mitochondrial localization When expressed in mammalian cells HyBak like 1 and 2 strongly induced apoptosis Six of the Bcl 2 family members inhibited apoptosis induced by camptothecin in mammalian cells with HyBcl 2 like 4 showing an especially strong protective effect This protein also interacted with HyBak like 1 in a yeast two hybrid assay Mutation of the conserved leucine in its BH3 domain abolished both the interaction with HyBak like 1 and the anti apoptotic effect Moreover we describe novel Hydra BH 3 only proteins One of these interacted with Bcl 2 like 4 and induced apoptosis in mammalian cells Our data indicate that the evolution

    Original URL path: http://www.cell-research.com/arts.asp?id=505 (2016-02-14)
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  • Cell Research
    SKLPPB National Plant Gene Research Centre College of Biological Sciences China Agricultural University no 2 West Yuan Ming Yuan Road Beijing 100193 China 2 National Institute of Biological Sciences Beijing 102206 China 3 Department of Biochemistry University of Alberta Alberta Canada 4 Crop Science Research Institute Chinese Academy of Agricultural Science Beijing 100081 China Correspondence Wei Hua Wu Tel 86 10 6273 1103 E mail wuwh public3 bta net cn Potassium transporters play crucial roles in K uptake and translocation in plants However so far little is known about the regulatory mechanism of potassium transporters Here we show that a Shaker like potassium channel AtKC1 encoded by the AtLKT1 gene cloned from the Arabidopsis thaliana low K LK tolerant mutant Atlkt1 significantly regulates AKT1 mediated K uptake under LK conditions Under LK conditions the Atkc1 mutants maintained their root growth whereas wild type plants stopped their root growth Lesion of AtKC1 significantly enhanced the tolerance of the Atkc1 mutants to LK stress and markedly increased K uptake and K accumulation in the Atkc1 mutant roots under LK conditions Electrophysiological results showed that AtKC1 inhibited the AKT1 mediated inward K currents and negatively shifted the voltage dependence of AKT1 channels These

    Original URL path: http://www.cell-research.com/arts.asp?id=506 (2016-02-14)
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  • Cell Research
    Chen 1 and Chengcai Chu 1 1 State Key Laboratory of Plant Genomics and National Center for Plant Gene Research Institute of Genetics and Developmental Biology Chinese Academy of Sciences Beijing 100101 China 2 Graduate School of the Chinese Academy of Sciences Beijing 100101 China Correspondence Chengcai Chu Tel 86 10 64877570 E mail ccchu genetics ac cn The architecture of the panicle including grain size and panicle morphology directly determines grain yield Panicle erectness which is selected for achieving ideal plant architecture in the northern part of China has drawn increasing attention of rice breeders Here dense and erect panicle 2 dep2 mutant which shows a dense and erect panicle phenotype was identified DEP2 encodes a plant specific protein without any known functional domain Expression profiling of DEP2 revealed that it is highly expressed in young tissues with most abundance in young panicles Morphological and expression analysis indicated that mutation in DEP2 mainly affects the rapid elongation of rachis and primary and secondary branches but does not impair the initiation or formation of panicle primordia Further analysis suggests that decrease of panicle length in dep2 is caused by a defect in cell proliferation during the exponential elongation of panicle

    Original URL path: http://www.cell-research.com/arts.asp?id=507 (2016-02-14)
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