ArticleRetrovirology2012
Phosphatase PPM1A negatively regulates P-TEFb function in resting CD4(+) T cells and inhibits HIV-1 gene expression.
Article in Retrovirology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- A comprehensive overview of PPM1A: From structure to disease.Experimental biology and medicine (Maywood, N.J.) · 2022Review
- MiR-1165-3p Suppresses Th2 Differentiation via Targeting IL-13 and PPM1A in a Mouse Model of Allergic Airway Inflammation.Allergy, asthma & immunology research · 2020Article
- P-TEFb as A Promising Therapeutic Target.Molecules (Basel, Switzerland) · 2020Review
- Targeting HIV-1 proviral transcription.Current opinion in virology · 2019Review
- Roles of CDKs in RNA polymerase II transcription of the HIV-1 genome.Transcription · 2019Review
- Cat and Mouse: HIV Transcription in Latency, Immune Evasion and Cure/Remission Strategies.Viruses · 2019Review
- Regulation of cyclin T1 during HIV replication and latency establishment in human memory CD4 T cells.Virology journal · 2019Article
- Cyclin-dependent kinase 7 (CDK7)-mediated phosphorylation of the CDK9 activation loop promotes P-TEFb assembly with Tat and proviral HIV reactivation.The Journal of biological chemistry · 2018Article
- The HIV-1 Tat Protein: Mechanism of Action and Target for HIV-1 Cure Strategies.Current pharmaceutical design · 2017Review
- Role of Host Factors on the Regulation of Tat-Mediated HIV-1 Transcription.Current pharmaceutical design · 2017Review
- Cyclin-dependent kinases as therapeutic targets for HIV-1 infection.Expert opinion on therapeutic targets · 2016Review
- Article
- Subversion of Cell Cycle Regulatory Mechanisms by HIV.Cell host & microbe · 2015Review
- Short communication: SAHA (vorinostat) induces CDK9 Thr-186 (T-loop) phosphorylation in resting CD4+ T cells: implications for reactivation of latent HIV.AIDS research and human retroviruses · 2015Article
- Transcriptional control of HIV latency: cellular signaling pathways, epigenetics, happenstance and the hope for a cure.Virology · 2014Review
- Viral-host interactions that control HIV-1 transcriptional elongation.Chemical reviews · 2013Review
- Reactivation of latent HIV: do all roads go through P-TEFb?Future virology · 2013Article
- Review
- Cyclin T1 and CDK9 T-loop phosphorylation are downregulated during establishment of HIV-1 latency in primary resting memory CD4+ T cells.Journal of virology · 2013Article
- CDK2 regulates HIV-1 transcription by phosphorylation of CDK9 on serine 90.Retrovirology · 2012Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundProcessive elongation of the integrated HIV-1 provirus is dependent on recruitment of P-TEFb by the viral Tat protein to the viral TAR RNA element. P-TEFb kinase activity requires phosphorylation of Thr186 in the T-loop of the CDK9 subunit. In resting CD4+T cells, low levels of T-loop phosphorylated CDK9 are found, which increase significantly upon activation. This suggests that the phosphorylation status of the T-loop is actively regulated through the concerted actions of cellular proteins such as Ser/Thr phosphatases. We investigated the role of phosphatase PPM1A in regulating CDK9 T-loop phosphorylation and its effect on HIV-1 proviral transcription.
resultsWe found that overexpression of PPM1A inhibits HIV-1 gene expression during viral infection and this required PPM1A catalytic function. Using an artificial CDK tethering system, we further found that PPM1A inhibits CDK9, but not CDK8 mediated activation of the HIV-1 LTR. SiRNA depletion of PPM1A in resting CD4+T cells increased the level of CDK9 T-loop phosphorylation and enhanced HIV-1 gene expression. We also observed that PPM1A protein levels are relatively high in resting CD4+T cells and are not up-regulated upon T cell activation.
conclusionsOur results establish a functional link between HIV-1 replication and modulation of CDK9 T-loop phosphorylation by PPM1A. PPM1A represses HIV-1 gene expression by inhibiting CDK9 T-loop phosphorylation, thus reducing the amount of active P-TEFb available for recruitment to the viral LTR. We also infer that PPM1A enzymatic activity in resting and activated CD4+ T cells are likely regulated by as yet undefined factors.
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