ArticleRetrovirology2012
CDK2 regulates HIV-1 transcription by phosphorylation of CDK9 on serine 90.
Article in Retrovirology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 51 citations in OpenAlex.
- Therapeutic modulation of HIV-1 using miRNAs and lncRNAs: from bench to bedside.Virology journal · 2026Review
- Cardiomyocyte Cyclin-dependent kinase 9 directly binds to and phosphorylates NF-κB p65 subunit to drive cardiac inflammation and remodeling.Nature communications · 2026Article
- Integrative Transcriptomic and Network Pharmacology Analysis Reveals Key Targets and Mechanisms ofPharmaceuticals (Basel, Switzerland) · 2025Article
- Cell-cycle-regulated transcriptional pausing ofMolecular biology of the cell · 2025Article
- Cell cycle-regulated transcriptional pausing ofbioRxiv : the preprint server for biology · 2024Article
- SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis.Signal transduction and targeted therapy · 2022Article
- When cyclin-dependent kinases meet viral infections, including SARS-CoV-2.Journal of medical virology · 2022Review
- HIV-1 infection in sickle cell disease and sickle cell trait: role of iron and innate response.Expert review of hematology · 2022Article
- Restriction of HIV-1 infection in sickle cell trait.Blood advances · 2021Article
- Microglia: The Real Foe in HIV-1-Associated Neurocognitive Disorders?Biomedicines · 2021Review
- CDK9: A Comprehensive Review of Its Biology, and Its Role as a Potential Target for Anti-Cancer Agents.Frontiers in oncology · 2021Review
- Long Non-coding RNAs Mechanisms of Action in HIV-1 Modulation and the Identification of Novel Therapeutic Targets.Non-coding RNA · 2020Review
- The Long Noncoding RNAmBio · 2019Article
- Specific ActivationJournal of virology · 2019Article
- Roles of CDKs in RNA polymerase II transcription of the HIV-1 genome.Transcription · 2019Review
- The Role of Macrophages in HIV-1 Persistence and Pathogenesis.Frontiers in microbiology · 2019Review
- RNA-induced epigenetic silencing inhibits HIV-1 reactivation from latency.Retrovirology · 2018Article
- HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription.Retrovirology · 2018Article
- Inhibition of HIV-1 infection in humanized mice and metabolic stability of protein phosphatase-1-targeting small molecule 1E7-03.Oncotarget · 2017Article
- Protein Phosphatase-1 -targeted Small Molecules, Iron Chelators and Curcumin Analogs as HIV-1 Antivirals.Current pharmaceutical design · 2017Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundHIV-1 transcription is activated by the viral Tat protein that recruits host positive transcription elongation factor-b (P-TEFb) containing CDK9/cyclin T1 to the HIV-1 promoter. P-TEFb in the cells exists as a lower molecular weight CDK9/cyclin T1 dimer and a high molecular weight complex of 7SK RNA, CDK9/cyclin T1, HEXIM1 dimer and several additional proteins. Our previous studies implicated CDK2 in HIV-1 transcription regulation. We also found that inhibition of CDK2 by iron chelators leads to the inhibition of CDK9 activity, suggesting a functional link between CDK2 and CDK9. Here, we investigate whether CDK2 phosphorylates CDK9 and regulates its activity.
resultsThe siRNA-mediated knockdown of CDK2 inhibited CDK9 kinase activity and reduced CDK9 phosphorylation. Stable shRNA-mediated CDK2 knockdown inhibited HIV-1 transcription, but also increased the overall level of 7SK RNA. CDK9 contains a motif (90SPYNR94) that is consensus CDK2 phosphorylation site. CDK9 was phosphorylated on Ser90 by CDK2 in vitro. In cultured cells, CDK9 phosphorylation was reduced when Ser90 was mutated to an Ala. Phosphorylation of CDK9 on Ser90 was also detected with phospho-specific antibodies and it was reduced after the knockdown of CDK2. CDK9 expression decreased in the large complex for the CDK9-S90A mutant and was correlated with a reduced activity and an inhibition of HIV-1 transcription. In contrast, the CDK9-S90D mutant showed a slight decrease in CDK9 expression in both the large and small complexes but induced Tat-dependent HIV-1 transcription. Molecular modeling showed that Ser 90 of CDK9 is located on a flexible loop exposed to solvent, suggesting its availability for phosphorylation.
conclusionOur data indicate that CDK2 phosphorylates CDK9 on Ser 90 and thereby contributes to HIV-1 transcription. The phosphorylation of Ser90 by CDK2 represents a novel mechanism of HIV-1 regulated transcription and provides a new strategy for activation of latent HIV-1 provirus.
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