title: A peptide inhibitor of exportin1 blocks shuttling of the adenoviral E1B 55 kDa protein but not export of viral late mRNAs.
abstract: The human subgroup C adenoviral E1B 55 kDa and E4 Orf6 proteins are required for efficient nuclear export of viral late mRNAs, but the cellular pathway that mediates such export has not been identified. As a first step to develop a general approach to address this issue, we have assessed the utility of cell-permeable peptide inhibitors of cellular export receptors. As both E1B and E4 proteins have been reported to contain a leucine-rich nuclear export signal (NES), we synthesized a cell-permeable peptide containing such an NES. This peptide induced substantial inhibition of export of the E1B protein, whereas a control, non-functional peptide did not. However, under the same conditions, the NES peptide had no effect on export of viral late mRNAs. These observations establish that viral late mRNAs are not exported by exportin1, as well as the value of peptide inhibitors in investigation of mRNA export regulation in adenovirus-infected cells.
authors.affiliation: Department of Molecular Biology, Princeton University, NJ 08544, USA. sjflint@molbio.princeton.edu
authors.forename: S J
authors.initials: SJ
authors.lastname: Flint
authors.forename: Wenying
authors.initials: W
authors.lastname: Huang
authors.forename: Joseph
authors.initials: J
authors.lastname: Goodhouse
authors.forename: Saw
authors.initials: S
authors.lastname: Kyin
mesh_terms: D017501:Adenovirus E1B Proteins / Q000187:drug effects* / Q000502:physiology; D000260:Adenoviruses, Human / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D000097606:Exportin 1 Protein
chemical_list: D017501:Adenovirus E1B Proteins; D028884:Karyopherins; D011480:Protease Inhibitors; D012333:RNA, Messenger; D012367:RNA, Viral; D018160:Receptors, Cytoplasmic and Nuclear; D014764:Viral Proteins; D000097606:Exportin 1 Protein