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dc.contributor.authorGu, Lili
dc.contributor.authorTsuji, Takahiro
dc.contributor.authorJarboui, Mohamed Ali
dc.contributor.authorYeo, Geok P
dc.contributor.authorSheehy, Noreen
dc.contributor.authorHall, William W
dc.contributor.authorGautier, Virginie W
dc.date.accessioned2011-07-13T09:42:34Z
dc.date.available2011-07-13T09:42:34Z
dc.date.issued2011
dc.identifier.citationIntermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: novel insights into the regulation of Rev nuclear import. 2011, 8:17 Retrovirologyen
dc.identifier.issn1742-4690
dc.identifier.pmid21401918
dc.identifier.doi10.1186/1742-4690-8-17
dc.identifier.urihttp://hdl.handle.net/10147/135955
dc.description.abstractThe HIV-1 regulatory protein Rev, which is essential for viral replication, mediates the nuclear export of unspliced viral transcripts. Rev nuclear function requires active nucleocytoplasmic shuttling, and Rev nuclear import is mediated by the recognition of its Nuclear Localisation Signal (NLS) by multiple import factors, which include transportin and importin β. However, it remains unclear which nuclear import pathway(s) predominate in vivo, and the cellular environment that modulates Rev nucleocytoplasmic shuttling remains to be characterised.
dc.description.abstractIn our study, we have identified the cellular protein HIC (Human I-mfa domain-Containing protein) as a novel interactor of HIV-1 Rev. We demonstrate that HIC selectively interferes with Rev NLS interaction with importin β and impedes its nuclear import and function, but does not affect Rev nuclear import mediated by transportin. Hence, the molecular determinants mediating Rev-NLS recognition by importin β and transportin appear to be distinct. Furthermore, we have employed HIC and M9 M, a peptide specifically designed to inhibit the transportin-mediated nuclear import pathway, to characterise Rev nuclear import pathways within different cellular environments. Remarkably, we could show that in 293T, HeLa, COS7, Jurkat, U937, THP-1 and CEM cells, Rev nuclear import is cell type specific and alternatively mediated by transportin or importin β, in a mutually exclusive fashion.
dc.description.abstractRev cytoplasmic sequestration by HIC may represent a novel mechanism for the control of Rev function. These studies highlight that the multivalent nature of the Rev NLS for different import receptors enables Rev to adapt its nuclear trafficking strategy.
dc.language.isoenen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/21401918en
dc.subject.meshActive Transport, Cell Nucleus
dc.subject.meshAnimals
dc.subject.meshCOS Cells
dc.subject.meshCell Line
dc.subject.meshCell Nucleus
dc.subject.meshCercopithecus aethiops
dc.subject.meshGene Expression Regulation, Viral
dc.subject.meshHIV-1
dc.subject.meshHela Cells
dc.subject.meshHumans
dc.subject.meshJurkat Cells
dc.subject.meshKaryopherins
dc.subject.meshMyogenic Regulatory Factors
dc.subject.meshNuclear Localization Signals
dc.subject.meshProtein Binding
dc.subject.meshU937 Cells
dc.subject.meshbeta Karyopherins
dc.subject.meshrev Gene Products, Human Immunodeficiency Virus
dc.titleIntermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: novel insights into the regulation of Rev nuclear import.en
dc.typeArticleen
dc.contributor.departmentUCD-Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin (UCD), Belfield, Dublin 4, Ireland.en
dc.identifier.journalRetrovirologyen
refterms.dateFOA2018-08-22T13:03:19Z
html.description.abstractThe HIV-1 regulatory protein Rev, which is essential for viral replication, mediates the nuclear export of unspliced viral transcripts. Rev nuclear function requires active nucleocytoplasmic shuttling, and Rev nuclear import is mediated by the recognition of its Nuclear Localisation Signal (NLS) by multiple import factors, which include transportin and importin β. However, it remains unclear which nuclear import pathway(s) predominate in vivo, and the cellular environment that modulates Rev nucleocytoplasmic shuttling remains to be characterised.
html.description.abstractIn our study, we have identified the cellular protein HIC (Human I-mfa domain-Containing protein) as a novel interactor of HIV-1 Rev. We demonstrate that HIC selectively interferes with Rev NLS interaction with importin β and impedes its nuclear import and function, but does not affect Rev nuclear import mediated by transportin. Hence, the molecular determinants mediating Rev-NLS recognition by importin β and transportin appear to be distinct. Furthermore, we have employed HIC and M9 M, a peptide specifically designed to inhibit the transportin-mediated nuclear import pathway, to characterise Rev nuclear import pathways within different cellular environments. Remarkably, we could show that in 293T, HeLa, COS7, Jurkat, U937, THP-1 and CEM cells, Rev nuclear import is cell type specific and alternatively mediated by transportin or importin β, in a mutually exclusive fashion.
html.description.abstractRev cytoplasmic sequestration by HIC may represent a novel mechanism for the control of Rev function. These studies highlight that the multivalent nature of the Rev NLS for different import receptors enables Rev to adapt its nuclear trafficking strategy.


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