HIV-1 Replication Is Inhibited by a Pseudo-substrate Peptide That Blocks Tat Transactivation
| Autor: | Takashi Okamoto, B M Peterlin, Hiroshi Okamoto, Thomas P. Cujec |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Gene Expression Regulation
Viral Transcriptional Activation biology Molecular Sequence Data RNA polymerase II Processivity Virus Replication Molecular biology Long terminal repeat Substrate Specificity Transactivation Viral replication Cyclin-dependent kinase Virology Gene Products tat HIV-1 biology.protein Humans tat Gene Products Human Immunodeficiency Virus Amino Acid Sequence Cyclin-dependent kinase 7 Peptides P-TEFb Protein Binding |
| Zdroj: | Virology. 270:337-344 |
| ISSN: | 0042-6822 |
| DOI: | 10.1006/viro.2000.0311 |
| Popis: | The activation of the HIV-1 long terminal repeat (LTR) by the viral transcriptional transactivator Tat is an essential step in the viral replication cycle. To increase the processivity of RNA polymerase II, Tat interacts with the positive transcription elongation factor b (P-TEFb) and cyclin-dependent kinase (CDK)-activating kinase (CAK). In this study, we demonstrate that a pseudo-substrate peptide for CDK7, mC2p, inhibits HIV-1 replication as well as Tat transactivation. Specifically, mC2p blocks only the activity of CAK and not that of P-TEFb. Moreover, mC2p inhibits Tat transactivation and HIV replication. Therefore, the activation of CDK7 by Tat is considered a critical step of Tat transactivation and mC2p and related compounds represent potential candidates for novel anti-HIV therapeutics. |
| Databáze: | OpenAIRE |
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