ArticleMolecular and cellular biology2012
Interaction of cyclin-dependent kinase 12/CrkRS with cyclin K1 is required for the phosphorylation of the C-terminal domain of RNA polymerase II.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 120 citations in OpenAlex.
- CDK12 promotes tumorigenesis but induces vulnerability to therapies inhibiting folate one-carbon metabolism in breast cancer.Nature communications · 2022Trial
- CDK12/13 inhibition overcomes platinum resistance by impairing RNA metabolism.Signal transduction and targeted therapy · 2026Article
- Targeting the Disease Response With NlpD and LytM for Effective Nonantibiotic Treatment of Urinary Tract Infections.The Journal of infectious diseases · 2026Article
- Discovery of CTX-439: A Potent and Selective CDK12 Inhibitor as a Prospective Anti-Cancer Drug.ACS medicinal chemistry letters · 2026Article
- Targeting CDK12 disrupts estrogen-receptor chromatin recruitment and ER-MED1 transcription in advanced ER+ breast cancer.Journal of the National Cancer Institute · 2026Article
- Dual Modes of Gene Regulation by CDK12.bioRxiv : the preprint server for biology · 2025Article
- Unbiased mapping of cereblon neosubstrate landscape by high-throughput proteomics.Nature communications · 2025Article
- Molecular consequences of acute versus chronic CDK12 loss in prostate carcinoma nominates distinct therapeutic strategies.bioRxiv : the preprint server for biology · 2025Article
- Mechanistic Roles of Transcriptional Cyclin-Dependent Kinases in Oncogenesis: Implications for Cancer Therapy.Cancers · 2025Review
- Dynamic O-GlcNAcylation and phosphorylation attract and expel proteins from RNA polymerase II to regulate mRNA maturation.Journal of biomedical science · 2025Article
- Absence of CDK12 in oocyte leads to female infertility.Cell death & disease · 2025Article
- Physiological and pathological roles of the transcriptional kinases CDK12 and CDK13 in the central nervous system.Cell death and differentiation · 2025Review
- Research Progress of PROTAC-Degraded CDKs in the Treatment of Breast Cancer.Breast cancer (Dove Medical Press) · 2025Review
- Synthetic Lethal Targeting of CDK12-Deficient Prostate Cancer with PARP Inhibitors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Transcription and DNA replication collisions lead to large tandem duplications and expose targetable therapeutic vulnerabilities in cancer.Nature cancer · 2024Article
- CDK12 loss drives prostate cancer progression, transcription-replication conflicts, and synthetic lethality with paralog CDK13.Cell reports. Medicine · 2024Article
- Identifying human pre-mRNA cleavage and polyadenylation factors by genome-wide CRISPR screens using a dual fluorescence readthrough reporter.Nucleic acids research · 2024Article
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- Large tandem duplications in cancer result from transcription and DNA replication collisions.medRxiv : the preprint server for health sciences · 2024Article
- Tubule-specific cyclin-dependent kinase 12 knockdown potentiates kidney injury through transcriptional elongation defects.International journal of biological sciences · 2024Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CrkRS (Cdc2-related kinase, Arg/Ser), or cyclin-dependent kinase 12 (CKD12), is a serine/threonine kinase believed to coordinate transcription and RNA splicing. While CDK12/CrkRS complexes were known to phosphorylate the C-terminal domain (CTD) of RNA polymerase II (RNA Pol II), the cyclin regulating this activity was not known. Using immunoprecipitation and mass spectrometry, we identified a 65-kDa isoform of cyclin K (cyclin K1) in endogenous CDK12/CrkRS protein complexes. We show that cyclin K1 complexes isolated from mammalian cells contain CDK12/CrkRS but do not contain CDK9, a presumed partner of cyclin K. Analysis of extensive RNA-Seq data shows that the 65-kDa cyclin K1 isoform is the predominantly expressed form across numerous tissue types. We also demonstrate that CDK12/CrkRS is dependent on cyclin K1 for its kinase activity and that small interfering RNA (siRNA) knockdown of CDK12/CrkRS or cyclin K1 has similar effects on the expression of a luciferase reporter gene. Our data suggest that cyclin K1 is the primary cyclin partner for CDK12/CrkRS and that cyclin K1 is required to activate CDK12/CrkRS to phosphorylate the CTD of RNA Pol II. These properties are consistent with a role of CDK12/CrkRS in regulating gene expression through phosphorylation of RNA Pol II.
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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.