ArticleRetrovirology2012
Identification of novel CDK9 and Cyclin T1-associated protein complexes (CCAPs) whose siRNA depletion enhances HIV-1 Tat function.
Article in Retrovirology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- CDK9 interacts with a RanGTP-importin-β complex to regulate erythroid enucleation.Journal of cell science · 2026Article
- PGRN is involved in macrophage M2 polarization regulation through TNFR2 in periodontitis.Journal of translational medicine · 2024Article
- P-TEFb is degraded by Siah1/2 in quiescent cells.Nucleic acids research · 2022Article
- Transcriptome Analysis Identifies Altered Biological Processes and Novel Markers in Human Immunodeficiency Virus-1 Long-Term Non-Progressors.Infection & chemotherapy · 2021Article
- BET inhibitors RVX-208 and PFI-1 reactivate HIV-1 from latency.Scientific reports · 2017Article
- Protein Phosphatase-1 -targeted Small Molecules, Iron Chelators and Curcumin Analogs as HIV-1 Antivirals.Current pharmaceutical design · 2017Review
- Biophysical Analysis of the N-Terminal Domain from the Human Protein Phosphatase 1 Nuclear Targeting Subunit PNUTS Suggests an Extended Transcription Factor TFIIS-Like Fold.The protein journal · 2016Article
- Reactivation of latent HIV-1 provirus via targeting protein phosphatase-1.Retrovirology · 2015Article
- Article
- Targeting HIV transcription: the quest for a functional cure.Current topics in microbiology and immunology · 2015Review
- Role of noncoding RNAs in the regulation of P-TEFb availability and enzymatic activity.BioMed research international · 2014Review
- Genotypic and phenotypic heterogeneity in the U3R region of HIV type 1 subtype C.AIDS research and human retroviruses · 2014Article
- HIV-1 transcription and latency: an update.Retrovirology · 2013Review
- Inhibition of HIV-1 transcription and replication by a newly identified cyclin T1 splice variant.The Journal of biological chemistry · 2013Article
- Effect of mimetic CDK9 inhibitors on HIV-1-activated transcription.Journal of molecular biology · 2013Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHIV-1 Tat activates RNA Polymerase II (RNAP II) elongation of the integrated provirus by recruiting a protein kinase known as P-TEFb to TAR RNA at the 5' end of nascent viral transcripts. The catalytic core of P-TEFb contains CDK9 and Cyclin T1 (CCNT1). A human endogenous complexome has recently been described - the set of multi-protein complexes in HeLa cell nuclei. We mined this complexome data set and identified 12 distinct multi-protein complexes that contain both CDK9 and CCNT1. We have termed these complexes CCAPs for CDK9/CCNT1-associated protein complexes. Nine CCAPs are novel, while three were previously identified as Core P-TEFb, the 7SK snRNP, and the Super-Elongation Complex. We have investigated the role of five newly identified CCAPs in Tat function and viral gene expression.
resultsWe examined five CCAPs that contain: 1) PPP1R10/TOX3/WDR82; 2) TTF2; 3) TPR; 4) WRNIP1; 5) FBXO11/CUL1/SKP1. SiRNA depletions of protein subunits of the five CCAPs enhanced Tat activation of an integrated HIV-1 LTR-Luciferase reporter in TZM-bl cells. Using plasmid transfection assays in HeLa cells, we also found that siRNA depletions of TTF2, FBXO11, PPP1R10, WDR82, and TOX3 enhanced Tat activation of an HIV-1 LTR-luciferase reporter, but the depletions did not enhance expression of an NF-κB reporter plasmid with the exception of PPP1R10. We found no evidence that depletion of CCAPs perturbed the level of CDK9/CCNT1 in the 7SK snRNP. We also found that the combination of siRNA depletions of both TTF2 and FBXO11 sensitized a latent provirus in Jurkat cells to reactivation by sub-optimal amounts of αCD3/CD28 antibodies.
conclusionsOur results identified five novel CDK9/CCNT1 complexes that are capable of negative regulation of HIV-1 Tat function and viral gene expression. Because siRNA depletions of CCAPs enhance Tat function, it is possible that these complexes reduce the level of CDK9 and CCNT1 available for Tat, similar to the negative regulation of Tat by the 7SK snRNP. Our results highlight the complexity in the biological functions of CDK9 and CCNT1.
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