ArticleThe Journal of biological chemistry2015
Expression, purification, and identification of associated proteins of the full-length hCDK12/CyclinK complex.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
30 citing papers in PubMed, 53 citations in OpenAlex.
- New insights into the dule roles CDK12 in human cancers: Mechanisms and interventions for cancer therapy.Journal of pharmaceutical analysis · 2025Review
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- Development of CDK12 as a Cancer Therapeutic Target and Related Inhibitors.Current cancer drug targets · 2025Review
- The Chronic Toxicity of Endocrine-Disrupting Chemical toInternational journal of molecular sciences · 2024Article
- CDK12 and Integrator-PP2A complex modulates LEO1 phosphorylation for processive transcription elongation.Science advances · 2023Article
- Article
- Discovery of a Highly Potent and Selective Dual PROTAC Degrader of CDK12 and CDK13.Journal of medicinal chemistry · 2022Article
- Review
- Disrupting the Molecular Pathway in Myotonic Dystrophy.International journal of molecular sciences · 2021Review
- CDK9 keeps RNA polymerase II on track.Cellular and molecular life sciences : CMLS · 2021Review
- CDK12 globally stimulates RNA polymerase II transcription elongation and carboxyl-terminal domain phosphorylation.Nucleic acids research · 2020Article
- CDK13 cooperates with CDK12 to control global RNA polymerase II processivity.Science advances · 2020Article
- CDK12 and PAK2 as novel therapeutic targets for human gastric cancer.Theranostics · 2020Article
- CDK12 Activity-Dependent Phosphorylation Events in Human Cells.Biomolecules · 2019Article
- Ex vivo screen identifies CDK12 as a metastatic vulnerability in osteosarcoma.The Journal of clinical investigation · 2019Article
- Selective Kinase Inhibition Shows That Bur1 (Cdk9) Phosphorylates the Rpb1 LinkerMolecular and cellular biology · 2019Article
- Human CDK12 and CDK13, multi-tasking CTD kinases for the new millenium.Transcription · 2019Review
- Mouse Model of Congenital Heart Defects, Dysmorphic Facial Features and Intellectual Developmental Disorders as a Result of Non-functional CDK13.Frontiers in cell and developmental biology · 2019Article
- CDK12: an emerging therapeutic target for cancer.Journal of clinical pathology · 2018Review
- Activation of the p53 Transcriptional Program Sensitizes Cancer Cells to Cdk7 Inhibitors.Cell reports · 2017Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
The coupling of transcription and associated processes has been shown to be dependent on the RNA polymerase II (RNAPII) C-terminal repeat domain (CTD) and the phosphorylation of the heptad repeats of which it is composed (consensus sequence Y1S2P3T4S5P6S7). Two primary S2 position CTD kinases have been identified in higher eukaryotes: P-TEFb and CDK12/CyclinK. The more recently discovered CDK12 appears to act at the 3'-end of the transcription unit and has been identified as a tumor suppressor for ovarian cancer; however much is still unknown about the in vivo roles of CDK12/CyclinK. In an effort to further characterize these roles we have purified to near homogeneity and characterized, full-length, active, human CDK12/CyclinK, and identified hCDK12-associated proteins via mass spectrometry. We find that employing a "2A" peptide-linked multicistronic construct containing CDK12 and CyclinK results in the efficient production of active, recombinant enzyme in the baculovirus/Sf9 expression system. Using GST-CTD fusion protein substrates we find that CDK12/CyclinK prefers a substrate with unmodified repeats or one that mimics prephosphorylation at the S7 position of the CTD; also the enzyme is sensitive to the inhibitor flavopiridol at higher concentrations. Identification of CDK12-associating proteins reveals a strong enrichment for RNA-processing factors suggesting that CDK12 affects RNA processing events in two distinct ways: Indirectly through generating factor-binding phospho-epitopes on the CTD of elongating RNAPII and directly through binding to specific factors.
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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.