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Cyclin T1 stabilizes expression levels of HIV‐1 Tat in cells
Author(s) -
Imai Kenichi,
Asamitsu Kaori,
Victoriano Ann Florence B.,
Cueno Marni E.,
Fujinaga Koh,
Okamoto Takashi
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.07424.x
Subject(s) - p tefb , transactivation , transcription (linguistics) , gene knockdown , small interfering rna , biology , microbiology and biotechnology , transcription factor , protein subunit , chemistry , rna , gene expression , gene , promoter , biochemistry , linguistics , philosophy
Transcription from HIV‐1 proviral DNA is a rate‐determining step for HIV‐1 replication. Interaction between the cyclin T1 (CycT1) subunit of positive transcription elongation factor b (P‐TEFb) and the Tat transactivator protein of HIV‐1 is crucial for viral transcription. CycT1 also interacts directly with the transactivation‐responsive element (TAR) located on the 5′end of viral mRNA, as well as with Tat through the Tat–TAR recognition motif (TRM). These molecular interactions represent a critical step for stimulation of HIV transcription. Thus, Tat and CycT1 are considered to be feasible targets for the development of novel anti‐HIV therapies. In this study, we demonstrate that CycT1 is positively involved in the Tat protein stability. Selective degradation of CycT1 by small interfering RNA (siRNA) culminated in proteasome‐mediated degradation of Tat and eventual inhibition of HIV‐1 gene expression. We noted that the siRNA‐mediated knockdown of CycT1 could inhibit HIV‐1 transcription without affecting cell viability and Tat mRNA levels. These findings clearly indicate that CycT1 is a feasible therapeutic target, and inactivation or depletion of CycT1 should effectively inhibit HIV replication by destabilizing Tat and suppressing Tat‐mediated HIV transcription.