ArticleNucleic acids research2012
PKC phosphorylates HEXIM1 and regulates P-TEFb activity.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 49 citations in OpenAlex.
- Phosphorylation of CDK9 at Ser175 enhances HIV transcription and is a marker of activated P-TEFb in CD4(+) T lymphocytes.PLoS pathogens · 2013Trial
- HEXIM1/P-TEFb complex controls RNA polymerase II pause release and immediate early gene induction following neuronal depolarization.The Journal of biological chemistry · 2026Article
- HEXIM1 inter-monomer autoinhibition governs 7SK RNA binding specificity and P-TEFb inactivation.Nature communications · 2026Article
- Single-molecule live imaging of subunit interactions and exchange within cellular regulatory complexes.Molecular cell · 2025Article
- The cell biology of HIV-1 latency and rebound.Retrovirology · 2024Review
- An alpha-herpesvirus employs host HEXIM1 to promote viral transcription.Journal of virology · 2024Article
- Progress in 7SK ribonucleoprotein structural biology.Frontiers in molecular biosciences · 2023Review
- CDK9 activity switch associated with AFF1 and HEXIM1 controls differentiation initiation from epidermal progenitors.Nature communications · 2022Article
- Disrupting the Cdk9/Cyclin T1 heterodimer of 7SK snRNP for the Brd4 and AFF1/4 guided reconstitution of active P-TEFb.Nucleic acids research · 2022Article
- Are BET Inhibitors yet Promising Latency-Reversing Agents for HIV-1 Reactivation in AIDS Therapy?Viruses · 2021Review
- CDK9: A Comprehensive Review of Its Biology, and Its Role as a Potential Target for Anti-Cancer Agents.Frontiers in oncology · 2021Review
- P-TEFb as A Promising Therapeutic Target.Molecules (Basel, Switzerland) · 2020Review
- Latency-Reversing Agents Induce Differential Responses in Distinct Memory CD4 T Cell Subsets in Individuals on Antiretroviral Therapy.Cell reports · 2019Article
- Activation of P-TEFb by cAMP-PKA signaling in autosomal dominant polycystic kidney disease.Science advances · 2019Article
- Microglial Cells: The Main HIV-1 Reservoir in the Brain.Frontiers in cellular and infection microbiology · 2019Review
- 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
- Bromodomain-containing protein 4-independent transcriptional activation by autoimmune regulator (AIRE) and NF-κB.The Journal of biological chemistry · 2018Article
- Hexim1, an RNA-controlled protein hub.Transcription · 2018Review
- SERPINB2 is regulated by dynamic interactions with pause-release proteins and enhancer RNAs.Molecular immunology · 2017Article
- Promising Role of Toll-Like Receptor 8 Agonist in Concert with Prostratin for Activation of Silent HIV.Journal of virology · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The positive transcription elongation factor b (P-TEFb) regulates RNA polymerase II elongation. In cells, P-TEFb partitions between small active and larger inactive states. In the latter, HEXIM1 binds to 7SK snRNA and recruits as well as inactivates P-TEFb in the 7SK snRNP. Several stimuli can affect this P-TEFb equilibrium. In this study, we demonstrate that protein kinase C (PKC) phosphorylates the serine at position158 (S158) in HEXIM1. This phosphorylated HEXIM1 protein neither binds to 7SK snRNA nor inhibits P-TEFb. Phorbol esters or the engagement of the T cell antigen receptor, which activate PKC and the expression of the constitutively active (CA) PKCθ protein, which is found in T cells, inhibit the formation of the 7SK snRNP. All these stimuli increase P-TEFb-dependent transcription. In contrast, the kinase-negative PKCθ and the mutant HEXIM1 (S158A) proteins block effects of these PKC-activating stimuli. These results indicate that the phosphorylation of HEXIM1 by PKC represents a major regulatory step of P-TEFb activity in cells.
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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.