[Transcription, Chromatin, and Epigenetics] I{kappa}B-{alpha} Represses the Transcriptional Activity of the HIV-1 Tat Transactivator by Promoting Its Nuclear Export

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[Transcription, Chromatin, and Epigenetics] I{kappa}B-{alpha} Represses the Transcriptional Activity of the HIV-1 Tat Transactivator by Promoting Its Nuclear Export

The long terminal repeat of human immunodeficiency virus, type 1 (HIV-1) contains an NF-B enhancer and is potently inhibited by IB-S32/36A, a proteolysis-resistant inhibitor of NF-B transacting factors. The evidence that NF-B is dispensable for HIV-1 expression raises the question of whether IB- represses the HIV-1 transcription by mechanisms distinct from NF-B inhibition. Here, we report that IB- negatively regulates the HIV-1 expression and replication in an NF-B-independent manner by directly binding to Tat, which results in the nuclear export and cytoplasmic sequestration of the viral transactivator. The sequence of IB- required for Tat inhibition spans from amino acids 72 to 287 and includes the nuclear localization signal, the carboxyl-terminal nuclear export signal, and the binding site for the arginine-rich domain of Tat. This novel mechanism of cross-talk between Tat and IB- provides further insights into the mechanisms of HIV-1 regulation and could assist in the development of novel strategies for AIDS therapy.