title: Viral-mediated stabilization of AU-rich element containing mRNA contributes to cell transformation.
abstract: E4orf6 is one of the oncogene products of adenovirus, and it also has an important role for transportation of cellular and viral messenger RNA (mRNA) during the late phase of virus infection. We previously revealed that E4orf6 controls the fate of AU-rich element (ARE) containing mRNA by perturbing the chromosome maintenance region 1-dependent export mechanism. Here, we show that E4orf6 stabilizes ARE-mRNA through the region required for its oncogenic activity and ubiquitin E3 ligase assembly. Cells that failed to stabilize ARE-mRNA after HuR knockdown were unable to produce colonies in soft agar, even when E4orf6 was expressed. Furthermore, the stabilized ARE-mRNA induced the transformation of rodent immortalized cells. These findings indicate that stabilized ARE-mRNA is necessary, if not all, for the oncogenic activity of E4orf6 and has the potential to transform cells, at least under a certain condition.
authors.affiliation: Department of Oral Pathology and Biology, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kuroshima
authors.forename: M
authors.initials: M
authors.lastname: Aoyagi
authors.forename: M
authors.initials: M
authors.lastname: Yasuda
authors.forename: T
authors.initials: T
authors.lastname: Kitamura
authors.forename: J P
authors.initials: JP
authors.lastname: Jehung
authors.forename: M
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Totsuka
authors.forename: M
authors.initials: M
authors.lastname: Shindoh
authors.forename: F
authors.initials: F
authors.lastname: Higashino
mesh_terms: D000256:Adenoviridae / Q000502:physiology*; D000257:Adenoviridae Infections / Q000150:complications / Q000235:genetics; D017504:Adenovirus E4 Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001482:Base Composition / Q000235:genetics / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D009687:Nuclear Proteins; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D017433:Protein Structure, Secondary / Q000502:physiology; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D020871:RNA Stability / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D051381:Rats; D050436:Regulatory Elements, Transcriptional / Q000235:genetics
chemical_list: C087425:ANP32A protein, human; D017504:Adenovirus E4 Proteins; C553318:E4orf6 protein, adenovirus; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins