Đang chuẩn bị nút TẢI XUỐNG, xin hãy chờ
Tải xuống
Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: Novel insights into the regulation of Rev nuclear impo. | Gu et al. Retrovirology 2011 8 17 http www.retrovirology.eom content 8 1 17 RETR0VIR0L0GY RESEARCH Open Access Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC Novel insights into the regulation of Rev nuclear import I I z 17-1-1 I -1- 1 7 ft A I I A I I I 1 I r 1 A I I I 1 I A I I I A I I I I I 1 Lili Gu Takahiro Tsuji Mohamed Ali Jarboui Geok P Yeo Noreen Sheehy William W Hall Virginie W Gautier 1 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 p. 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 p 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 p 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 p in a mutually exclusive fashion. Conclusions Rev cytoplasmic sequestration by HIC may represent a novel mechanism for the control of Rev function. These studies .
