ArticleeLife2021
Reversible phosphorylation of cyclin T1 promotes assembly and stability of P-TEFb.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Human chromatin remodelers regulating HIV-1 transcription: a target for small molecule inhibitors.Epigenetics & chromatin · 2025Review
- A Truncated Isoform of Cyclin T1 Could Contribute to the Non-Permissive HIV-1 Phenotype of U937 Promonocytic Cells.Viruses · 2024Article
- The cell biology of HIV-1 latency and rebound.Retrovirology · 2024Review
- More than a decade of genetic research on the Denisovans.Nature reviews. Genetics · 2024Review
- Newly developed preclinical models reveal broad-spectrum CDK inhibitors as potent drugs for CRPC exhibiting primary resistance to enzalutamide.Cancer science · 2024Article
- Targeting CDK9 with selective inhibitors or degraders in tumor therapy: an overview of recent developments.Cancer biology & therapy · 2023Review
- Article
- A CRISPR Screen of HIV Dependency Factors Reveals ThatViruses · 2023Article
- A CRISPR screen of HIV dependency factors revealsbioRxiv : the preprint server for biology · 2023Article
- P-TEFb: The master regulator of transcription elongation.Molecular cell · 2023Review
- New insights into transcription elongation control of HIV-1 latency and rebound.Trends in immunology · 2023Review
- hnRNP R negatively regulates transcription by modulating the association of P-TEFb with 7SK and BRD4.EMBO reports · 2022Article
- P-TEFb is degraded by Siah1/2 in quiescent cells.Nucleic acids research · 2022Article
- AKAP1 contributes to impaired mtDNA replication and mitochondrial dysfunction in podocytes of diabetic kidney disease.International journal of biological sciences · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The positive transcription elongation factor b (P-TEFb) is a critical coactivator for transcription of most cellular and viral genes, including those of HIV. While P-TEFb is regulated by 7SK snRNA in proliferating cells, P-TEFb is absent due to diminished levels of CycT1 in quiescent and terminally differentiated cells, which has remained unexplored. In these cells, we found that CycT1 not bound to CDK9 is rapidly degraded. Moreover, productive CycT1:CDK9 interactions are increased by PKC-mediated phosphorylation of CycT1 in human cells. Conversely, dephosphorylation of CycT1 by PP1 reverses this process. Thus, PKC inhibitors or removal of PKC by chronic activation results in P-TEFb disassembly and CycT1 degradation. This finding not only recapitulates P-TEFb depletion in resting CD4+ T cells but also in anergic T cells. Importantly, our studies reveal mechanisms of P-TEFb inactivation underlying T cell quiescence, anergy, and exhaustion as well as proviral latency and terminally differentiated 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.