Inhibition of Tat activity by the HEXIM1 protein.
Details
Serval ID
serval:BIB_E1C5F86006ED
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Inhibition of Tat activity by the HEXIM1 protein.
Journal
Retrovirology
ISSN
1742-4690[electronic]
Publication state
Published
Issued date
2005
Volume
2
Pages
42
Language
english
Abstract
BACKGROUND: The positive transcription elongation factor b (P-TEFb) composed by CDK9/CyclinT1 subunits is a dedicated co-factor of HIV transcriptional transactivator Tat protein. Transcription driven by the long terminal repeat (LTR) of HIV involves formation of a quaternary complex between P-TEFb, Tat and the TAR element. This recruitment is necessary to enhance the processivity of RNA Pol II from the HIV-1 5' LTR promoter. The activity of P-TEFb is regulated in vivo and in vitro by the HEXIM1/7SK snRNA ribonucleic-protein complex. RESULTS: Here we report that Tat transactivation is effectively inhibited by co-expression of HEXIM1 or its paralog HEXIM2. HEXIM1 expression specifically represses transcription mediated by the direct activation of P-TEFb through artificial recruitment of GAL4-CycT1. Using appropriate HEXIM1 mutants we determined that effective Tat-inhibition entails the 7SK snRNA basic recognition motif as well as the C-terminus region required for interaction with cyclin T1. Enhanced expression of HEXIM1 protein modestly affects P-TEFb activity, suggesting that HEXIM1-mediated repression of Tat activity is not due to a global inhibition of cellular transcription. CONCLUSION: These results point to a pivotal role of P-TEFb for Tat's optimal transcription activity and suggest that cellular proteins that regulate P-TEFb activity might exert profound effects on Tat function in vivo.
Keywords
Animals, CHO Cells, Cell Line, Cricetinae, Gene Expression Regulation, Viral, Gene Products, tat/antagonists &, inhibitors, Gene Products, tat/genetics, Humans, Positive Transcriptional Elongation Factor B/genetics, Positive Transcriptional Elongation Factor B/metabolism, Protein Binding, RNA, Small Nuclear/metabolism, RNA-Binding Proteins/genetics, RNA-Binding Proteins/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
28/07/2008 16:57
Last modification date
20/08/2019 17:05