title: The adenovirus type 5 E1B-55K oncoprotein is a highly active shuttle protein and shuttling is independent of E4orf6, p53 and Mdm2.
abstract: The E1B-55K and E4orf6 oncoproteins of adenovirus type 5 are involved in the export of viral mRNAs. Previously, it was suggested that a complex composed of E1B-55K and E4orf6 serves as a nucleocytoplasmic transporter for viral mRNAs in which the E4orf6 protein directs both nuclear import and export. We now demonstrate that the E1B-55K protein itself shuttles efficiently in the absence of E4orf6. In addition, E1B-55K trafficking was independent of the defined shuttle proteins Mdm2 or p53, which interacts with E1B-55K. The identified N-terminal E1B-55K leucine-rich nuclear-export signal (NES) conferred rapid nuclear export even in a heterologous system in contrast to the postulated E4orf6NES. Interestingly, although shuttling was blocked by inhibitors of the CRM1 mediated export pathway, E1B-55K inhibited neither the activity nor the trafficking of the retroviral shuttle proteins HIV-1 Rev and HTLV-1 Rex. In contrast, Rev or Rex blocked the nuclear export of E1B-55K, most likely by competing for essential export factors. Our results provide new insights into the regulation of the adenovirus mRNA export system and the processes of adenovirus mediated transformation. Oncogene (2000) 19, 850 - 857.
authors.affiliation: Institute for Clinical and Molecular Virology, University of Erlangen-Nürnberg, Schlossgarten 4, D-91054 Erlangen, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Krätzer
authors.forename: O
authors.initials: O
authors.lastname: Rosorius
authors.forename: P
authors.initials: P
authors.lastname: Heger
authors.forename: N
authors.initials: N
authors.lastname: Hirschmann
authors.forename: T
authors.initials: T
authors.lastname: Dobner
authors.forename: J
authors.initials: J
authors.lastname: Hauber
authors.forename: R H
authors.initials: RH
authors.lastname: Stauber
mesh_terms: D016475:3T3 Cells; D017501:Adenovirus E1B Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D017504:Adenovirus E4 Proteins / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000502:physiology; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins; D051379:Mice; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals / Q000502:physiology; D009687:Nuclear Proteins; D016366:Open Reading Frames; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051736:Proto-Oncogene Proteins c-mdm2; D018160:Receptors, Cytoplasmic and Nuclear; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014709:Vero Cells; D000097606:Exportin 1 Protein
chemical_list: D017501:Adenovirus E1B Proteins; D017504:Adenovirus E4 Proteins; D002352:Carrier Proteins; D028884:Karyopherins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D018160:Receptors, Cytoplasmic and Nuclear; D016159:Tumor Suppressor Protein p53; D000097606:Exportin 1 Protein; C497206:MDM2 protein, human; C497207:Mdm2 protein, mouse