title: Nuclear export of cutaneous HPV8 E7 oncoprotein is mediated by a leucine-rich nuclear export signal via a CRM1 pathway.
abstract: We recently determined that the nuclear import of cutaneous beta genus HPV8 E7 oncoprotein it is mediated by its zinc-binding domain via direct hydrophobic interactions with the FG nucleoporins Nup62 and Nup153 (Onder and Moroianu, 2014). Here we investigated the nuclear export of HPV8 E7 oncoprotein using confocal microscopy after transfections of HeLa cells with EGFP-8cE7 and mutant plasmids and treatment with Ratjadone A nuclear export inhibitor. We determined that HPV8 E7 contains a leucine-rich nuclear export signal (NES), 76IRTFQELLF84, within its zinc-binding domain that mediates its nuclear export via a CRM1 pathway. We found that HPV8 E7 interacts with CRM1 and that the hydrophobic amino acid residues I76, F79 and L82 of the NES are essential for this interaction and for nuclear export of HPV8 E7 oncoprotein.
authors.affiliation: Biology Department, Boston College, Chestnut Hill, MA 02467, USA.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Onder
authors.affiliation: Biology Department, Boston College, Chestnut Hill, MA 02467, USA.
authors.forename: Vivian
authors.initials: V
authors.lastname: Chang
authors.affiliation: Biology Department, Boston College, Chestnut Hill, MA 02467, USA. Electronic address: moroianu@bc.edu.
authors.forename: Junona
authors.initials: J
authors.lastname: Moroianu
mesh_terms: D021581:Active Transport, Cell Nucleus; D019943:Amino Acid Substitution; D052686:Betapapillomavirus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D006367:HeLa Cells; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000502:physiology; D006801:Humans; D028884:Karyopherins / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D049790:Nuclear Export Signals / Q000235:genetics / Q000502:physiology; D050725:Papillomavirus E7 Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000209:etiology / Q000821:virology; D000097606:Exportin 1 Protein
chemical_list: D028884:Karyopherins; D049790:Nuclear Export Signals; D050725:Papillomavirus E7 Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D000097606:Exportin 1 Protein
keywords: CRM1; Cutaneous HPV8 E7 oncoprotein; Nuclear export