title: Functional analysis of the C-terminal region of human adenovirus E1A reveals a misidentified nuclear localization signal.
abstract: The immortalizing function of the human adenovirus 5 E1A oncoprotein requires efficient localization to the nucleus. In 1987, a consensus monopartite nuclear localization sequence (NLS) was identified at the C-terminus of E1A. Since that time, various experiments have suggested that other regions of E1A influence nuclear import. In addition, a novel bipartite NLS was recently predicted at the C-terminal region of E1A in silico. In this study, we used immunofluorescence microscopy and co-immunoprecipitation analysis with importin-α to verify that full nuclear localization of E1A requires the well characterized NLS spanning residues 285-289, as well as a second basic patch situated between residues 258 and 263 ((258)RVGGRRQAVECIEDLLNEPGQPLDLSCKRPRP(289)). Thus, the originally described NLS located at the C-terminus of E1A is actually a bipartite signal, which had been misidentified in the existing literature as a monopartite signal, altering our understanding of one of the oldest documented NLSs.
authors.affiliation: Department of Microbiology & Immunology, The University of Western Ontario, A4-833 London Regional Cancer Centre, 800 Commissioners Road E., London, Ontario, N6A 4L6 Canada.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cohen
authors.affiliation: Department of Microbiology & Immunology, The University of Western Ontario, A4-833 London Regional Cancer Centre, 800 Commissioners Road E., London, Ontario, N6A 4L6 Canada.
authors.forename: Cason R
authors.initials: CR
authors.lastname: King
authors.affiliation: Department of Microbiology & Immunology, The University of Western Ontario, A4-833 London Regional Cancer Centre, 800 Commissioners Road E., London, Ontario, N6A 4L6 Canada.
authors.forename: Jimmy D
authors.initials: JD
authors.lastname: Dikeakos
authors.affiliation: Department of Microbiology & Immunology, The University of Western Ontario, A4-833 London Regional Cancer Centre, 800 Commissioners Road E., London, Ontario, N6A 4L6 Canada; Department of Oncology, The University of Western Ontario, London Regional Cancer Centre, Ontario, Canada. Electronic address: jmymryk@uwo.ca.
authors.forename: Joe S
authors.initials: JS
authors.lastname: Mymryk
mesh_terms: D017500:Adenovirus E1A Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000260:Adenoviruses, Human / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D002460:Cell Line; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals / Q000502:physiology*
chemical_list: D017500:Adenovirus E1A Proteins; D019913:Nuclear Localization Signals
keywords: Adenovirus; E1A; Nuclear localization signals