ArticleMolecular and cellular biology2009
TFIIH-associated Cdk7 kinase functions in phosphorylation of C-terminal domain Ser7 residues, promoter-proximal pausing, and termination by RNA polymerase II.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 226 papers.
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Who cites it
226 citing papers in PubMed, 344 citations in OpenAlex.
- RNA polymerase II phosphorylation dynamics: from molecular mechanisms to human disease.RNA biology · 2026Review
- Inhibition of CDK12/CDK13-CYCLIN K rewires P-TEFb signaling to reverse HIV-1 latency and modulate cellular gene expression.EMBO molecular medicine · 2026Article
- Sensitizing tumor response to topoisomerase I antibody-drug conjugate by selective CDK7 inhibition.Science advances · 2026Article
- Communication is key: combinatorial phosphorylation and functional cross-talk in the RNA polymerase II CTD code.Biochemical Society transactions · 2026Review
- Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026Review
- The Role of Transcriptional and Atypical Cyclin-Dependent Protein Kinases in Melanoma.Cancers · 2026Review
- Article
- Oncogene c‑Myc: From molecular mechanism to targeted therapy (Review).Molecular medicine reports · 2026Review
- Phosphorylation of SF3B1 by CDK11 orchestrates spliceosome activation via SNIP1-dependent RES complex recruitment.Nature communications · 2026Article
- An epigenetic bifunctional that toggles between transactivation and repression.bioRxiv : the preprint server for biology · 2026Article
- Disrupting CDK9 activity suppresses triple-negative breast cancer and is enhanced by EGFR Inhibition.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Histone H2B monoubiquitylation regulates elongation-to-termination transition in RNA polymerase II transcription.Communications biology · 2025Article
- Single-molecule Microscopy Reveals That TFIIE Subunits Dynamically Interact With Preinitiation Complexes in a Manner Impacted by TFIIH.Journal of molecular biology · 2025Article
- Article
- CDK7-CDK11 axis in spliceosome regulation and pre-mRNA splicing.Nucleic acids research · 2025Article
- Review
- Recent advances in development of CDK7 inhibitors and their clinical trials: a narrative review.Translational cancer research · 2025Review
- Exploiting targeted degradation of cyclins and cyclin-dependent kinases for cancer therapeutics: a review.Journal of Zhejiang University. Science. B · 2025Review
- Multi-omics and biochemical reconstitution reveal CDK7-dependent mechanisms controlling RNA polymerase II function at gene 5'- and 3' ends.Cell reports · 2025Article
- Targeting CDK7/12/13 functional synergism reverses myofibroblast activation and ameliorates lung fibrosis.iScience · 2025Article
166 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The function of human TFIIH-associated Cdk7 in RNA polymerase II (Pol II) transcription and C-terminal domain (CTD) phosphorylation was investigated in analogue-sensitive Cdk7(as/as) mutant cells where the kinase can be inhibited without disrupting TFIIH. We show that both Cdk7 and Cdk9/PTEFb contribute to phosphorylation of Pol II CTD Ser5 residues on transcribed genes. Cdk7 is also a major kinase of CTD Ser7 on Pol II at the c-fos and U snRNA genes. Furthermore, TFIIH and recombinant Cdk7-CycH-Mat1 as well as recombinant Cdk9-CycT1 phosphorylated CTD Ser7 and Ser5 residues in vitro. Inhibition of Cdk7 in vivo suppressed the amount of Pol II accumulated at 5' ends on several genes including c-myc, p21, and glyceraldehyde-3-phosphate dehydrogenase genes, indicating reduced promoter-proximal pausing or polymerase "leaking" into the gene. Consistent with a 5' pausing defect, Cdk7 inhibition reduced recruitment of the negative elongation factor NELF at start sites. A role of Cdk7 in regulating elongation is further suggested by enhanced histone H4 acetylation and diminished histone H4 trimethylation on lysine 36-two marks of elongation-within genes when the kinase was inhibited. Consistent with a new role for TFIIH at 3' ends, it was detected within genes and 3'-flanking regions, and Cdk7 inhibition delayed pausing and transcription termination.
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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.