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- Title
Inhibition of Tat activity by the HEXIM1 protein.
- Authors
Fraldi, Alessandro; Varrone, Francesca; Napolitano, Giuliana; Michels, Annemieke A.; Majello, Barbara; Bensaude, Olivier; Lania, Luigi
- 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.
- Subjects
AIDS; HIV infections; HIV; HIV-positive persons; VIRUS diseases; NUCLEIC acids
- Publication
Retrovirology, 2005, Vol 2, p42
- ISSN
1742-4690
- Publication type
Article
- DOI
10.1186/1742-4690-2-42