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/10147/126931
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
Citation:
Retrovirology. 2011 Mar 14;8(1):17
Issue Date:
14-Mar-2011
URI:
http://hdl.handle.net/10147/126931
Abstract:
Abstract Background 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. Results 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. Conclusions 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:
Journal Article

Full metadata record

DC FieldValue Language
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.accessioned2011-04-04T09:21:45Z-
dc.date.available2011-04-04T09:21:45Z-
dc.date.issued2011-03-14-
dc.identifierhttp://dx.doi.org/10.1186/1742-4690-8-17-
dc.identifier.citationRetrovirology. 2011 Mar 14;8(1):17-
dc.identifier.urihttp://hdl.handle.net/10147/126931-
dc.description.abstractAbstract Background 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. Results 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. Conclusions 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.-
dc.titleIntermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: Novel insights into the regulation of Rev nuclear import.-
dc.typeJournal Article-
dc.language.rfc3066en-
dc.rights.holderGu et al.; licensee BioMed Central Ltd.-
dc.description.statusPeer Reviewed-
dc.date.updated2011-03-30T05:01:10Z-
All Items in Lenus, The Irish Health Repository are protected by copyright, with all rights reserved, unless otherwise indicated.