title: The nuclear protein Sam68 is redistributed to the cytoplasm and is involved in PI3K/Akt activation during EV71 infection.
abstract: Nuclear proteins can be triggered to be redistributed to the cytoplasm to assist with EV71 virus replication. This process is frequently involved in cellular signal transduction upon virus infection. In this study, we have demonstrated that a new nuclear protein, 68-kDa Src-associated in mitosis protein (Sam68), was translocated to the cytoplasm and was co-localized with EV71 during virus infection. Confocal microscopy and subcellular fractionation assay confirmed that virus 3C protease triggered the redistribution of Sam68 to the cytoplasm. Knockdown of Sam68 expression using ShRNA significantly inhibited virus replication, suggesting that Sam68 may be a host factor involved in EV71 life cycle. In addition, EV71-induced Akt phosphorylation involved a PI3K-dependent mechanism. Sam68 is known to be an upstream regulator of PI3K and our immunoprecipitation studies confirmed that Sam68 interacted directly with the p85 regulatory subunit of PI3K and mediated PI3K/Akt activation during EV71 infection. On the contrary, silencing of Sam68 dramatically abrogated Akt phosphorylation. These data, plus the fact that Sam68 is known to be a signaling adaptor protein, indicated that Sam68 is a signal molecule with a functional role in the PI3K/Akt signal pathway during EV71 infection.
authors: Center for Molecular Virology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China; College of Life Science and Technology, HeiLongJiang BaYi Agricultural University, Daqing 163319, China.
authors: Hua
authors: H
authors: Zhang
authors: Center for Molecular Virology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Haolong
authors: H
authors: Cong
authors: Center for Molecular Virology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Lei
authors: L
authors: Song
authors: Center for Molecular Virology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: tienpo@sun.im.ac.cn.
authors: Po
authors: P
authors: Tien
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D003593:Cytoplasm / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029821:Enterovirus A, Human / Q000502:physiology*; D004847:Epithelial Cells / Q000821:virology; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D018613:Microscopy, Confocal; D021381:Protein Transport; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C489559:KHDRBS1 protein, human; D016601:RNA-Binding Proteins; D058543:Class Ia Phosphatidylinositol 3-Kinase
keywords: EV71; PI3K/Akt signal pathway; Sam68; Virus replication