ArticleThe Journal of biological chemistry2011
Expression of a protein phosphatase 1 inhibitor, cdNIPP1, increases CDK9 threonine 186 phosphorylation and inhibits HIV-1 transcription.
Article in The Journal of biological chemistry, 2011. 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, 47 citations in OpenAlex.
- Article
- Article
- Emerging roles of the Protein Phosphatase 1 (PP1) in the context of viral infections.Cell communication and signaling : CCS · 2024Review
- Alprazolam Prompts HIV-1 Transcriptional Reactivation and Enhances CTL Response Through RUNX1 Inhibition and STAT5 Activation.Frontiers in neurology · 2021Article
- Structural Optimization of 2,3-Dihydro-1H-cyclopenta[ACS infectious diseases · 2020Article
- Review
- Genome-Wide Identification of Long Non-Coding RNAs and Their Regulatory Networks Involved inInsects · 2019Article
- Phosphorylated VP30 of Marburg Virus Is a Repressor of TranscriptionJournal of virology · 2018Article
- 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
- Miklós Bodanszky Award Lecture: Advances in the selective targeting of protein phosphatase-1 and phosphatase-2A with peptides.Journal of peptide science : an official publication of the European Peptide Society · 2017Review
- Inhibition of HIV-1 infection in humanized mice and metabolic stability of protein phosphatase-1-targeting small molecule 1E7-03.Oncotarget · 2017Article
- MD simulation of the Tat/Cyclin T1/CDK9 complex revealing the hidden catalytic cavity within the CDK9 molecule upon Tat binding.PloS one · 2017Article
- Protein Phosphatase-1 -targeted Small Molecules, Iron Chelators and Curcumin Analogs as HIV-1 Antivirals.Current pharmaceutical design · 2017Review
- Role of Host Factors on the Regulation of Tat-Mediated HIV-1 Transcription.Current pharmaceutical design · 2017Review
- Increased iron export by ferroportin induces restriction of HIV-1 infection in sickle cell disease.Blood advances · 2016Article
- Article
- Cracking the control of RNA polymerase II elongation by 7SK snRNP and P-TEFb.Nucleic acids research · 2016Review
- Protein Phosphatases Involved in Regulating Mitosis: Facts and Hypotheses.Molecules and cells · 2016Review
- LncRNApred: Classification of Long Non-Coding RNAs and Protein-Coding Transcripts by the Ensemble Algorithm with a New Hybrid Feature.PloS one · 2016Article
- Genome-wide characterization of long intergenic non-coding RNAs (lincRNAs) provides new insight into viral diseases in honey bees Apis cerana and Apis mellifera.BMC genomics · 2015Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
CDK9/cyclin T1, a key enzyme in HIV-1 transcription, is negatively regulated by 7SK RNA and the HEXIM1 protein. Dephosphorylation of CDK9 on Thr(186) by protein phosphatase 1 (PP1) in stress-induced cells or by protein phosphatase M1A in normally growing cells activates CDK9. Our previous studies showed that HIV-1 Tat protein binds to PP1 through the Tat Q(35)VCF(38) sequence, which is similar to the PP1-binding RVXF motif and that this interaction facilitates HIV-1 transcription. In the present study, we analyzed the effect of expression of the central domain of nuclear inhibitor of PP1 (cdNIPP1) in an engineered cell line and also when cdNIPP1 was expressed as part of HIV-1 pNL4-3 in place of nef. Stable expression of cdNIPP1 increased CDK9 phosphorylation on Thr(186) and the association of CDK9 with 7SK RNA. The stable expression of cdNIPP1 disrupted the interaction of Tat and PP1 and inhibited HIV-1 transcription. Expression of cdNIPP1 as a part of the HIV-1 genome inhibited HIV-1 replication. Our study provides a proof-of-concept for the future development of PP1-targeting compounds as inhibitors of HIV-1 replication.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.