Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: novel insights into the regulation of Rev nuclear import.

Hdl Handle:
http://hdl.handle.net/10147/135955
Title:
Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: novel insights into the regulation of Rev nuclear import.
Authors:
Gu, Lili; Tsuji, Takahiro; Jarboui, Mohamed Ali; Yeo, Geok P; Sheehy, Noreen; Hall, William W; Gautier, Virginie W
Affiliation:
UCD-Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin (UCD), Belfield, Dublin 4, Ireland.
Citation:
Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: novel insights into the regulation of Rev nuclear import. 2011, 8:17 Retrovirology
Journal:
Retrovirology
Issue Date:
2011
URI:
http://hdl.handle.net/10147/135955
DOI:
10.1186/1742-4690-8-17
PubMed ID:
21401918
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed/21401918
Abstract:
The 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.; In 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.; Rev 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.
Item Type:
Article
Language:
en
MeSH:
Active Transport, Cell Nucleus; Animals; COS Cells; Cell Line; Cell Nucleus; Cercopithecus aethiops; Gene Expression Regulation, Viral; HIV-1; Hela Cells; Humans; Jurkat Cells; Karyopherins; Myogenic Regulatory Factors; Nuclear Localization Signals; Protein Binding; U937 Cells; beta Karyopherins; rev Gene Products, Human Immunodeficiency Virus
ISSN:
1742-4690

Full metadata record

DC FieldValue Language
dc.contributor.authorGu, Lilien
dc.contributor.authorTsuji, Takahiroen
dc.contributor.authorJarboui, Mohamed Alien
dc.contributor.authorYeo, Geok Pen
dc.contributor.authorSheehy, Noreenen
dc.contributor.authorHall, William Wen
dc.contributor.authorGautier, Virginie Wen
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
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