title: Identification and characterization of multiple conserved nuclear localization signals within adenovirus E1A.
abstract: The human adenovirus 5 (HAdV-5) E1A protein has a well defined canonical nuclear localization signal (NLS) located at its C-terminus. We used a genetic assay in the yeast Saccharomyces cerevisiae to demonstrate that the canonical NLS is present and functional in the E1A proteins of each of the six HAdV species. This assay also detects a previously described non-canonical NLS within conserved region 3 and a novel active NLS within the N-terminal/conserved region 1 portion of HAdV-5 E1A. These activities were also present in the E1A proteins of each of the other five HAdV species. These results demonstrate that, despite substantial differences in primary sequence, HAdV E1A proteins are remarkably consistent in that they contain one canonical and two non-canonical NLSs. By utilizing independent mechanisms, these multiple NLSs ensure nuclear localization of E1A in the infected cell.
authors.affiliation: Department of Microbiology & Immunology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6.
authors.forename: Kris S
authors.initials: KS
authors.lastname: Marshall
authors.affiliation: Department of Microbiology & Immunology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cohen
authors.affiliation: Department of Microbiology & Immunology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6.
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Fonseca
authors.affiliation: Department of Microbiology & Immunology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6.
authors.forename: Biljana
authors.initials: B
authors.lastname: Todorovic
authors.affiliation: Department of Microbiology & Immunology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6.
authors.forename: Cason R
authors.initials: CR
authors.lastname: King
authors.affiliation: Department of Chemical and Environmental Engineering, Masdar Institute, Abu Dhabi, United Arab Emirates.
authors.forename: Ahmed F
authors.initials: AF
authors.lastname: Yousef
authors.affiliation: College of Animal Science and Technologies, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Microbiology & Immunology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6; Department of Oncology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6. Electronic address: jmymryk@uwo.ca.
authors.forename: Joe S
authors.initials: JS
authors.lastname: Mymryk
mesh_terms: D017500:Adenovirus E1A Proteins / Q000235:genetics*; D000260:Adenoviruses, Human / Q000235:genetics*; D006801:Humans; D019913:Nuclear Localization Signals; D012441:Saccharomyces cerevisiae / Q000235:genetics
chemical_list: D017500:Adenovirus E1A Proteins; D019913:Nuclear Localization Signals
keywords: Adenovirus; E1A; Importin; NPI1; Nuclear import; Qip1; Rch1