Affinage

CDK19

Cyclin-dependent kinase 19 · UniProt Q9BWU1

Length
502 aa
Mass
56.8 kDa
Annotated
2026-04-28
100 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CDK19 is a cyclin-dependent kinase that, together with its paralog CDK8, assembles with cyclin C (CCNC), MED12, and MED13 into a mutually exclusive kinase module that reversibly associates with the Mediator complex to regulate RNA polymerase II–dependent transcription (PMID:30585107). Although CDK8 and CDK19 share qualitative effects on phosphorylation and gene expression, CDK19 can operate through a kinase-independent scaffolding mechanism—exemplified during IFN-γ responses, where CDK8 drives Pol II pause release via its kinase activity while CDK19 regulates distinct gene sets without requiring catalytic function—and both kinases protect cyclin C from degradation (PMID:31495563, PMID:37378433). CDK19 interacts with p53 to suppress p21 transcription, thereby sustaining proliferation of hematopoietic stem cells and prostate epithelial cells; acting redundantly with CDK8, it phosphorylates SWI/SNF components to control lineage-specifying enhancers in the intestinal epithelium, phosphorylates Drp1 to promote mitochondrial fission in neurons, and modulates STAT5 signaling in immune cell differentiation (PMID:35110726, PMID:36006697, PMID:38637532, PMID:40795210). De novo missense variants in CDK19 that alter kinase activity cause a neurodevelopmental epileptic encephalopathy syndrome, as demonstrated by failure of variant alleles to rescue Drosophila Cdk8 loss-of-function phenotypes (PMID:32330417, PMID:33495529).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2008 Medium

    Establishing that CDK19 assembles into Mediator complexes distinct from CDK8-containing complexes resolved whether the two paralogs were interchangeable subunits, revealing they can exert opposing transcriptional effects.

    Evidence Affinity purification of epitope-tagged CDK19-containing complexes and siRNA knockdown with VP16-dependent reporter assays in human cells

    PMID:18651850

    Open questions at the time
    • Single reporter system; genome-wide transcriptional targets of CDK19-specific complexes not identified
    • Opposing functions not mechanistically explained
  2. 2010 Medium

    Linking CDK19 haploinsufficiency to a neurodevelopmental phenotype in a human patient and showing reduced dendritic branching upon Drosophila cdk8 knockdown established CDK19 as a candidate neurodevelopmental disease gene with a neuronal morphological function.

    Evidence Chromosomal breakpoint mapping (FISH, qPCR) in a patient with microcephaly and mental retardation; conditional Drosophila cdk8 knockdown in multiple dendrite neurons with morphological analysis

    PMID:20563892

    Open questions at the time
    • Single patient—causality versus association not fully resolved
    • Drosophila cdk8 is ortholog of both CDK8 and CDK19, so paralog-specific contribution unclear
  3. 2015 High

    Development of a highly selective CDK8/CDK19 chemical probe (CCT251545) and identification of STAT1-Ser727 phosphorylation as a biomarker provided essential pharmacological tools to dissect CDK8/CDK19 kinase function in cells and in vivo.

    Evidence X-ray crystallography of CDK8-inhibitor complex, kinase selectivity profiling against 291 kinases, cell-based and in vivo tumor model assays

    PMID:26502155

    Open questions at the time
    • Probe inhibits both CDK8 and CDK19 equally—cannot distinguish paralog-specific contributions
    • Structural basis for CDK19 binding inferred from CDK8 crystal structure
  4. 2018 High

    Consolidation of biochemical evidence defined the Mediator kinase module architecture—CDK8 or CDK19 mutually exclusively paired with CCNC, MED12, and MED13—and clarified that the kinases regulate Pol II transcription indirectly by phosphorylating transcription factors and modulating Mediator structure.

    Evidence Biochemical complex characterization and synthesis of genetic/biochemical evidence across multiple laboratories

    PMID:30585107

    Open questions at the time
    • Structural basis for mutual exclusivity between CDK8 and CDK19 not resolved
    • Full substrate repertoire of the kinase module unknown
  5. 2019 High

    Chemical-genetic decoupling revealed that CDK8 and CDK19 regulate distinct gene sets during IFN-γ signaling through fundamentally different mechanisms—CDK8 via kinase-dependent Pol II pause release and CDK19 via kinase-independent scaffolding—resolving a long-standing question about functional redundancy versus specialization.

    Evidence GRO-seq, PRO-seq, cortistatin A treatment, and CDK8/CDK19 decoupling in human cells

    PMID:31495563

    Open questions at the time
    • Scaffolding partners mediating CDK19 kinase-independent function not identified
    • Whether kinase-independent function of CDK19 generalizes beyond IFN-γ signaling unclear
  6. 2019 Medium

    Demonstrating that CDK8/CDK19 kinase inhibition promotes Treg differentiation by sensitizing TGF-β/Smad2/3 signaling while attenuating IFN-γ/STAT1 signaling established the kinase module as a regulator of immune cell fate decisions.

    Evidence CDK8/CDK19 inhibitors in Treg differentiation assays, phospho-signaling analysis, and EAE mouse model

    PMID:31552016

    Open questions at the time
    • CDK19-specific versus CDK8-specific contribution to Treg biology not separated
    • Direct kinase substrates in Treg signaling not biochemically confirmed
  7. 2020 High

    Functional complementation in Drosophila proved that de novo CDK19 missense variants (Y32H, T196A) are pathogenic loss-of-function alleles causing a neurodevelopmental epileptic encephalopathy, establishing CDK19 as a bona fide disease gene.

    Evidence Human CDK19 wild-type and variant cDNA rescue of Drosophila Cdk8 null (lethality, seizures, NMJ morphology assays)

    PMID:32330417

    Open questions at the time
    • Whether variants act through loss of kinase activity, scaffolding, or both not determined
    • Mammalian model of CDK19 variant pathogenicity not yet established
  8. 2021 High

    In vitro kinase assays revealed that disease-associated CDK19 variants differentially alter enzymatic activity—G28R reducing and Y32H increasing kinase activity—demonstrating that pathogenesis involves dysregulated catalytic function beyond simple loss-of-function.

    Evidence In vitro autophosphorylation and substrate phosphorylation assays with recombinant CDK19 variants; zebrafish morphological validation

    PMID:33495529

    Open questions at the time
    • Physiological substrates affected by altered kinase activity in neurons not identified
    • Whether gain-of-kinase-activity (Y32H) and loss-of-kinase-activity (G28R) converge on the same downstream pathway unclear
  9. 2022 High

    Genetic studies in mouse intestine demonstrated that CDK8 and CDK19 act redundantly to phosphorylate SWI/SNF complex components and maintain SWI/SNF and MED12-Mediator co-occupancy at lineage-specifying enhancers, revealing a direct mechanistic link between the kinase module and chromatin remodeling at tissue-specific regulatory elements.

    Evidence Conditional CDK8/CDK19 double knockout mice, ChIP-seq, co-immunoprecipitation, phosphorylation assays in intestinal epithelial cells

    PMID:36006697

    Open questions at the time
    • Specific SWI/SNF phosphorylation sites targeted by CDK8/CDK19 not fully mapped
    • Whether SWI/SNF phosphorylation mechanism operates in non-intestinal tissues unknown
  10. 2022 Medium

    Identification of CDK19 interaction with p53 to suppress p21 transcription revealed a non-Mediator mechanism by which CDK19 sustains hematopoietic stem cell proliferation and self-renewal.

    Evidence CDK19 knockout mice, Co-IP of CDK19–p53, CDK8/19 inhibitor treatment, p53 inhibitor rescue in HSCs and AML cells

    PMID:35110726

    Open questions at the time
    • Direct binding interface between CDK19 and p53 not structurally characterized
    • Whether CDK19–p53 interaction is kinase-dependent or scaffolding-dependent not resolved
  11. 2023 High

    Multi-omic analysis resolved the long-standing redundancy question by showing CDK8 and CDK19 have qualitatively identical effects on phosphoproteome and transcriptome, with differential phenotypes arising from expression-level differences; both kinases additionally protect cyclin C from degradation in a kinase-independent manner.

    Evidence Transcriptomics, proteomics, and phosphoproteomics in isogenic CDK8/CDK19 knockout, inhibitor-treated, and PROTAC-degraded cell lines

    PMID:37378433

    Open questions at the time
    • Mechanism of kinase-independent cyclin C stabilization not defined
    • Whether qualitative redundancy holds in all tissue contexts remains untested
  12. 2024 High

    Demonstrating that CDK8/CDK19 phosphorylates Drp1 at Ser616 in the cytoplasm to promote mitochondrial fission in neurons, and that this pathway intersects with PINK1 signaling, linked the kinase module to mitochondrial dynamics and neurodegeneration-relevant biology.

    Evidence Drosophila neuronal Cdk8 loss-of-function, endogenous GFP-tagged Cdk8 localization, Drp1-S616 phosphorylation assay, human CDK19 rescue, genetic interaction with Pink1

    PMID:38637532

    Open questions at the time
    • Whether CDK19 directly phosphorylates Drp1 in mammalian neurons not shown
    • Cytoplasmic CDK19 pool versus Mediator-associated pool not quantified
  13. 2025 Medium

    Studies in immune cells established that CDK8/CDK19 regulate STAT5 phosphorylation to activate ILC2s (driving lung fibrosis) and to control Treg/effector T-cell balance, with CDK8/CDK19 inhibition also reprogramming T-cell metabolism away from glycolysis.

    Evidence CDK8/19 inhibitors in ILC2-deficient mice, OVA asthma models, STAT5 blockade rescue, transcriptomics, and metabolic assays

    PMID:40795210 PMID:41770851

    Open questions at the time
    • Whether CDK8/CDK19 directly phosphorylates STAT5 or acts through an intermediate kinase not resolved
    • CDK19-specific contribution versus CDK8 not separated in these immune contexts
  14. 2025 Medium

    Extending the CDK19–p53 axis, CDK19 was shown to be transcriptionally driven by GRHL2 in prostate epithelium, where CDK19 sequesters p53 to suppress p21 and maintain proliferative capacity; aging-related GRHL2 loss releases p53 from CDK19, triggering senescence.

    Evidence Single-nucleus transcriptomics, CDK19–p53 complex analysis, GRHL2 gene therapy in aged prostate, in vivo aging model

    PMID:41266629

    Open questions at the time
    • Direct biochemical evidence for CDK19 sequestration of p53 (stoichiometry, binding domain) remains limited
    • Whether this mechanism operates in tissues beyond prostate and HSCs not tested
  15. 2025 Medium

    Functional complementation in Drosophila muscle confirmed that human CDK19 substitutes for Cdk8, with disease variant T196A failing to rescue muscle and mitochondrial phenotypes, extending CDK19 disease biology beyond neurons to striated muscle.

    Evidence Drosophila RNAi cdk8 depletion, human CDK19 wild-type/variant complementation, muscle morphology, mitochondrial morphology, behavioral assays

    PMID:41251503

    Open questions at the time
    • No mammalian muscle model of CDK19 variants tested
    • Discrepancy between Y32H rescue in muscle but gain-of-kinase-activity in vitro not explained
  16. 2026 High

    Identifying CDK8/CDK19 as essential host cofactors for hepatitis delta virus RNA replication—required for Pol II CTD phosphorylation during RNA-templated transcription—established a non-canonical role for the kinase module in viral genome expression.

    Evidence CDK8/19 inhibitor and genetic CDK8/CDK19 knockouts in HDV replication assays across multiple cell models, Pol II CTD phosphorylation analysis, HDAg rescue

    PMID:41665877

    Open questions at the time
    • Whether CDK8 versus CDK19 contributes differentially to HDV replication not resolved
    • Mechanism by which small HDAg bypasses CDK8/CDK19 requirement not fully elucidated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include the structural basis for CDK19-specific scaffolding function, the identity of CDK19-specific versus CDK8-specific substrates in different tissues, the precise mechanism of CDK19–p53 interaction, and whether disease-associated gain-of-kinase and loss-of-kinase CDK19 variants converge on a common pathogenic pathway.
  • No crystal structure of CDK19 kinase module
  • Comprehensive CDK19-specific substrate identification lacking
  • No mammalian knock-in model of CDK19 disease variants

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0098772 molecular function regulator activity 4 GO:0140110 transcription regulator activity 4 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 1
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-1643685 Disease 3 R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-4839726 Chromatin organization 1
Partners
CCNCDRP1MED12MED13STAT1STAT5TP53
Complex memberships
Mediator complex (reversible association)Mediator kinase module (CDK8/CDK19–CCNC–MED12–MED13)

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 CCT251545 is a potent and selective chemical probe for CDK8 and CDK19 with >100-fold selectivity over 291 other kinases; X-ray crystallography demonstrates a type 1 binding mode involving insertion of the CDK8 C-terminus into the ligand binding site. STAT1(Ser727) phosphorylation was identified as a biomarker of CDK8/CDK19 kinase activity in vitro and in vivo. X-ray crystallography, kinase selectivity profiling, cell-based assays, in vivo tumor models Nature chemical biology High 26502155
2018 CDK8 and CDK19 are incorporated mutually exclusively into a 4-protein kinase module (with CCNC, MED12, MED13) that reversibly associates with the Mediator complex; CCNC and MED12 activate CDK8/CDK19 kinase function, and MED13 enables their association with Mediator. The Mediator kinases phosphorylate transcription factors and control Mediator structure/function to indirectly regulate RNA Pol II transcription. Biochemical complex characterization, review of genetic and biochemical evidence Transcription High 30585107
2019 CDK8 and CDK19 regulate different gene sets via mechanistically distinct functions in response to IFN-γ: CDK8-dependent regulation requires its kinase activity and promotes RNA Pol II pause release, whereas CDK19 governs IFN-γ responses through a kinase-independent scaffolding function. CDK8, not CDK19, phosphorylates STAT1 transcription factor during IFN-γ stimulation. GRO-seq, PRO-seq, cortistatin A chemical genetics, transcriptomics, chemical-genetic CDK8/CDK19 decoupling Molecular cell High 31495563
2008 Human CDK11 (hereafter treated as a distinct paralog from CDK19) forms Mediator complexes devoid of CDK8, and siRNA knockdown revealed that CDK8 and CDK11 (CDK19) have opposing functions in VP16-dependent transcriptional regulation. Affinity purification of epitope-tagged hCDK11-containing complexes, siRNA knockdown, luciferase reporter assay Genes to cells Medium 18651850
2019 CDK8 and its homologous kinase CDK19 are required for BMP4-induced epithelial-to-mesenchymal transition (EMT) in cancer; both genetic and pharmacological inhibition of CDK8/CDK19 abrogates BMP-induced EMT, tumor cell invasion, and YAP nuclear localization through SMAD1-dependent signaling. Genetic inhibition (siRNA/shRNA), pharmacological inhibition, in vitro invasion assays, in vivo syngeneic EMT model, RNA-seq Oncogene Medium 29780169
2019 CDK8 and CDK19 have the same qualitative effects on protein phosphorylation and gene expression; differential effects of CDK8 vs CDK19 knockouts are attributable to quantitative differences in expression/activity rather than different functions. Both enzymes protect their binding partner cyclin C from proteolytic degradation in a kinase-independent manner. Transcriptomics, proteomics, phosphoproteomics using genetic modifications, CDK8/19 inhibitors, and CDK8/19 PROTAC degrader Nucleic acids research High 37378433
2019 Inhibition of CDK8/CDK19 kinase activity promotes differentiation of regulatory T (Treg) cells and expression of Foxp3, CTLA4, PD-1, and GITR by sensitizing TGF-β signaling (enhanced phospho-Smad2/3) and attenuating IFN-γ-STAT1 signaling. Small molecule CDK8/CDK19 inhibitors, Treg differentiation assays, phospho-signaling analysis, EAE mouse model Frontiers in immunology Medium 31552016
2022 CDK8 and CDK19 function redundantly to regulate intestinal lineage specification; the Mediator kinase module phosphorylates key components of the chromatin remodeling complex SWI/SNF in intestinal epithelial cells, and SWI/SNF and MED12-Mediator colocalize at lineage-specifying enhancers in a CDK8/19-dependent manner. Genetically defined mouse models, pharmacological inhibitors, ChIP-seq, co-immunoprecipitation, phosphorylation assays Journal of Clinical Investigation High 36006697
2022 CDK8 and CDK19 act redundantly to control expression of the CFTR pathway in the intestinal epithelium; combined deletion reduces long-term proliferative capacity and downregulates CFTR expression, and pharmacological CDK8/19 inhibition recapitulates these phenotypes. Double CDK8/CDK19 knockout intestinal organoids and mice, pharmacological CDK8/19 inhibition, gene expression analysis EMBO reports High 36545778
2022 CDK19 regulates proliferation of hematopoietic stem cells (HSCs) and AML cells by suppressing p53-mediated transcription of p21; CDK19 interacts with p53 to inhibit p53-mediated transcription of p21, and CDK19 knockout mice show activated p53 signaling in HSCs with impaired proliferation and self-renewal. CDK19 knockout mice, Co-IP (CDK19-p53 interaction), CDK8/19 inhibitor (SenexinB), p53 inhibitor rescue experiments, CDK19 overexpression Leukemia Medium 35110726
2020 De novo missense variants in CDK19 (p.Tyr32His and p.Thr196Ala) cause a neurodevelopmental syndrome; human CDK19 reference cDNA rescues loss of Drosophila Cdk8 (larval lethality, seizures, NMJ bouton/synapse loss), but the disease-associated variants fail to rescue and behave as null alleles. Drosophila Cdk8 knockout complementation with human CDK19 wild-type and variant cDNA; NMJ morphology, seizure, lifespan assays American Journal of Human Genetics High 32330417
2021 De novo missense CDK19 variants at Gly28 and Tyr32 have altered kinase activity: Gly28Arg reduces kinase activity, while Tyr32His increases kinase activity relative to wild-type (as shown by autophosphorylation and substrate phosphorylation assays); both cause morphological abnormalities in zebrafish, indicating pathogenetic mechanisms beyond simple loss-of-function. In vitro autophosphorylation assay, substrate phosphorylation assay, in vivo zebrafish mRNA injection morphological assay Genetics in medicine High 33495529
2021 CDK19 activity promotes O-GlcNAcylation and YAP expression in liver cancer cells; corosolic acid inhibits CDK19 activity and thereby reduces OGT-mediated O-GlcNAcylation and YAP expression, and CDK19 overexpression reverses CA-induced decreases. CDK19 overexpression/inhibition, western blot for O-GlcNAcylation and YAP, xenotransplantation model Cell death & disease Low 34588426
2024 Drosophila Cdk8 (ortholog of human CDK8 and CDK19) promotes mitochondrial fission through phosphorylation of Drp1 at Ser616 in the cytoplasm; human CDK19 rescues neuronal loss-of-Cdk8 phenotypes (reduced lifespan, bang sensitivity, elongated mitochondria), and Cdk8 loss-of-function phenotypically overlaps with Pink1 deficiency, with Cdk8 overexpression suppressing Pink1 phenotypes. Drosophila neuronal Cdk8 loss-of-function, endogenous GFP-tagged Cdk8 localization, Drp1-S616 phosphorylation assay, human CDK19 rescue, genetic interaction with Pink1 Nature communications High 38637532
2025 CDK8 and CDK19 (acting via STAT5 phosphorylation) are required for activation of group 2 innate lymphoid cells (ILC2s), driving lung fibrosis; CDK8/19 inhibitor AS3334366 suppresses serine phosphorylation of STAT5 in ILC2s and ameliorates OVA-induced lung fibrosis in mice. CDK8/19 inhibitor in OVA asthma mouse model, ILC2-deficient mice, cytokine stimulation assays, STAT5 phosphorylation analysis Journal of immunology Medium 40795210
2025 CDK8/CDK19 inhibition (AS2863619) promotes conversion of CD4+ effector T cells into Foxp3+ Tregs by augmenting STAT5 phosphorylation and suppressing STAT3 phosphorylation; this Treg-promoting activity is critically dependent on STAT5 signaling, and CDK8/CDK19 inhibition also induces metabolic reprogramming (suppressing glycolysis) in T cells. Small molecule CDK8/CDK19 inhibitor, STAT5 blockade experiments, transcriptomic analysis, metabolic functional analysis, murine ITP model Blood Medium 41770851
2026 CDK8 and CDK19 are essential cofactors for hepatitis delta virus (HDV) replication; CDK8/19 activity is required for Pol II phosphorylation during HDV RNA-templated transcription, and loss of CDK8/19 activity (pharmacological or knockout) completely prevents establishment of HDV replication. Ectopic expression of small HDAg (but not its methylation site R13 mutant) restores HDV replication in CDK8/19-deficient cells. CDK8/19 inhibitor (MSC2530818), genetic CDK8/CDK19 knockouts, HDV replication assays in multiple cell culture models, Pol II CTD phosphorylation analysis Hepatology High 41665877
2025 In young prostate epithelial cells, GRHL2 promotes CDK19 transcription, and CDK19 sequesters p53 to suppress p21Waf1/Cip1 expression, maintaining cell proliferation. Aging-related downregulation of GRHL2 releases p53 from the CDK19-p53 complex, activating p21Waf1/Cip1 and inducing senescence. Single-nucleus transcriptomics, histological analyses, protein complex analysis (CDK19-p53), gene therapy (GRHL2 re-expression), in vivo prostate aging model Nature aging Medium 41266629
2025 Cdk8/CDK19 (Drosophila cdk8 ortholog) loss causes thicker muscle myofibrils, fused mitochondria, and climbing defects; expression of wild-type human CDK19 rescues these defects in cdk8-depleted flies, while the disease-associated T196A variant fails to rescue (loss-of-function), and Y32H can rescue, suggesting functional conservation between Drosophila Cdk8 and human CDK19. Drosophila RNAi cdk8 depletion, human CDK19 wild-type and variant complementation, muscle morphology, mitochondrial morphology, behavioral assays Human molecular genetics Medium 41251503
2025 CDK8 and CDK19 are required for normal macrophage differentiation; double CDK8/CDK19 knockout macrophages show increased expression of M1-like and M2-like markers, altered cytokine secretion, deregulated gene expression, precocious cell cycle exit, and impaired Fc-mediated phagocytosis. Double knockout (DKO) hematopoietic Cdk8/Cdk19 mice, bone marrow-derived macrophage differentiation assays, gene expression analysis, phagocytosis assay Cell cycle Medium 41123539
2010 CDK19 (then described as disrupted in a patient with microcephaly, retinal folds, and mental retardation) is expressed in fetal eye and fetal brain; haploinsufficiency due to chromosomal breakpoint at 6q21 disrupting CDK19 causes ~50% reduction in transcript. In Drosophila, conditional knockdown of the CDK19 ortholog (cdk8) in multiple dendrite neurons resulted in reduced dendritic branching and altered dendritic arbor morphology. Karyotyping, FISH, qPCR, Drosophila cdk8 conditional knockdown in MD neurons with morphological analysis Human genetics Medium 20563892

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 CDK11 complexes promote pre-mRNA splicing. The Journal of biological chemistry 124 12501247
2015 A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease. Nature chemical biology 123 26502155
2008 Characterization of cyclin L1 and L2 interactions with CDK11 and splicing factors: influence of cyclin L isoforms on splice site selection. The Journal of biological chemistry 102 18216018
2018 Regulatory functions of the Mediator kinases CDK8 and CDK19. Transcription 100 30585107
2016 Pan-Cancer Analysis of the Mediator Complex Transcriptome Identifies CDK19 and CDK8 as Therapeutic Targets in Advanced Prostate Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 89 27678455
2016 Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19. Journal of medicinal chemistry 87 26796641
2004 Failure to proliferate and mitotic arrest of CDK11(p110/p58)-null mutant mice at the blastocyst stage of embryonic cell development. Molecular and cellular biology 75 15060143
2019 Transcriptional Responses to IFN-γ Require Mediator Kinase-Dependent Pause Release and Mechanistically Distinct CDK8 and CDK19 Functions. Molecular cell 72 31495563
2022 CDK11 regulates pre-mRNA splicing by phosphorylation of SF3B1. Nature 70 36104565
2008 Cdk11 is a RanGTP-dependent microtubule stabilization factor that regulates spindle assembly rate. The Journal of cell biology 70 18316407
2007 CDK11(p58) is required for the maintenance of sister chromatid cohesion. Journal of cell science 70 17606997
2014 Targeting CDK11 in osteosarcoma cells using the CRISPR-Cas9 system. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 65 25348612
2012 Systematic kinome shRNA screening identifies CDK11 (PITSLRE) kinase expression is critical for osteosarcoma cell growth and proliferation. Clinical cancer research : an official journal of the American Association for Cancer Research 64 22791884
2002 Casein kinase 2 interacts with cyclin-dependent kinase 11 (CDK11) in vivo and phosphorylates both the RNA polymerase II carboxyl-terminal domain and CDK11 in vitro. The Journal of biological chemistry 63 12429741
2016 The emerging roles and therapeutic potential of cyclin-dependent kinase 11 (CDK11) in human cancer. Oncotarget 62 27049727
2019 Molecular and in vivo Functions of the CDK8 and CDK19 Kinase Modules. Frontiers in cell and developmental biology 57 30693281
2015 Cyclin-dependent kinase 11(p110) (CDK11(p110)) is crucial for human breast cancer cell proliferation and growth. Scientific reports 53 25990212
2018 Mediator kinase CDK8/CDK19 drives YAP1-dependent BMP4-induced EMT in cancer. Oncogene 52 29780169
2019 Long noncoding RNA CASC2 promotes paclitaxel resistance in breast cancer through regulation of miR-18a-5p/CDK19. Histochemistry and cell biology 50 31352515
2015 CDK11 in TREX/THOC Regulates HIV mRNA 3' End Processing. Cell host & microbe 49 26567509
2010 CDK19 is disrupted in a female patient with bilateral congenital retinal folds, microcephaly and mild mental retardation. Human genetics 49 20563892
2013 Cyclin-dependent kinase 11 (CDK11) is crucial in the growth of liposarcoma cells. Cancer letters 48 24007862
2012 Cdk11-cyclinL controls the assembly of the RNA polymerase II mediator complex. Cell reports 48 23122962
2009 HIV-1 mRNA 3' end processing is distinctively regulated by eIF3f, CDK11, and splice factor 9G8. Molecular cell 45 19854136
2020 CDK11 is required for transcription of replication-dependent histone genes. Nature structural & molecular biology 42 32367068
2020 Galactosyltransferase B4GALT1 confers chemoresistance in pancreatic ductal adenocarcinomas by upregulating N-linked glycosylation of CDK11p110. Cancer letters 40 33309857
2023 CDK8 and CDK19: positive regulators of signal-induced transcription and negative regulators of Mediator complex proteins. Nucleic acids research 37 37378433
2019 Inhibition of Cdk8/Cdk19 Activity Promotes Treg Cell Differentiation and Suppresses Autoimmune Diseases. Frontiers in immunology 37 31552016
2016 Cyclin-Dependent Kinase 11 (CDK11) Is Required for Ovarian Cancer Cell Growth In Vitro and In Vivo, and Its Inhibition Causes Apoptosis and Sensitizes Cells to Paclitaxel. Molecular cancer therapeutics 37 27207777
2020 De Novo Variants in CDK19 Are Associated with a Syndrome Involving Intellectual Disability and Epileptic Encephalopathy. American journal of human genetics 36 32330417
2019 Increased mediator complex subunit CDK19 expression associates with aggressive prostate cancer. International journal of cancer 31 31271443
2011 The cyclin-dependent kinase PITSLRE/CDK11 is required for successful autophagy. Autophagy 31 21808150
2011 CDK11(p58) is required for centriole duplication and Plk4 recruitment to mitotic centrosomes. PloS one 30 21297952
2008 Human mediator kinase subunit CDK11 plays a negative role in viral activator VP16-dependent transcriptional regulation. Genes to cells : devoted to molecular & cellular mechanisms 30 18651850
2012 CHK2 kinase promotes pre-mRNA splicing via phosphorylating CDK11(p110). Oncogene 26 23178491
2021 Corosolic acid inhibits cancer progression by decreasing the level of CDK19-mediated O-GlcNAcylation in liver cancer cells. Cell death & disease 25 34588426
2005 Downregulation of beta1,4-galactosyltransferase 1 inhibits CDK11(p58)-mediated apoptosis induced by cycloheximide. Biochemical and biophysical research communications 24 15629159
2018 The Emerging Picture of CDK11: Genetic, Functional and Medicinal Aspects. Current medicinal chemistry 22 28814241
2011 Polypyrimidine tract-binding protein regulates the cell cycle through IRES-dependent translation of CDK11(p58) in mouse embryonic stem cells. Cell cycle (Georgetown, Tex.) 22 22037210
2020 CircRNA-1926 Promotes the Differentiation of Goat SHF Stem Cells into Hair Follicle Lineage by miR-148a/b-3p/CDK19 Axis. Animals : an open access journal from MDPI 21 32887226
2022 CDK19 regulates the proliferation of hematopoietic stem cells and acute myeloid leukemia cells by suppressing p53-mediated transcription of p21. Leukemia 20 35110726
2022 Hotair promotes the migration and proliferation in ovarian cancer by miR-222-3p/CDK19 axis. Cellular and molecular life sciences : CMLS 19 35451651
2019 CDK11p110 plays a critical role in the tumorigenicity of esophageal squamous cell carcinoma cells and is a potential drug target. Cell cycle (Georgetown, Tex.) 18 30722725
2011 Mislocalization of CDK11/PITSLRE, a regulator of the G2/M phase of the cell cycle, in Alzheimer disease. Cellular & molecular biology letters 18 21461981
2010 Thr-370 is responsible for CDK11(p58) autophosphorylation, dimerization, and kinase activity. The Journal of biological chemistry 17 21078675
2014 CDK11(p58) kinase activity is required to protect sister chromatid cohesion at centromeres in mitosis. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 16 24436071
2023 CDK11 requires a critical activator SAP30BP to regulate pre-mRNA splicing. The EMBO journal 15 38059508
2022 Crystal structure of the CDK11 kinase domain bound to the small-molecule inhibitor OTS964. Structure (London, England : 1993) 15 36327972
2021 CDK19-related disorder results from both loss-of-function and gain-of-function de novo missense variants. Genetics in medicine : official journal of the American College of Medical Genetics 15 33495529
2015 Critical role of CDK11(p58) in human breast cancer growth and angiogenesis. BMC cancer 15 26470709
2007 CDK11(p58) protein kinase activity is associated with Bcl-2 down-regulation in pro-apoptosis pathway. Molecular and cellular biochemistry 15 17516030
2024 Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila. Nature communications 14 38637532
2023 Therapeutic potential of CDK11 in cancer. Clinical and translational medicine 14 36855776
2022 Hsa_circ_0006692 Promotes Lung Cancer Progression via miR-205-5p/CDK19 Axis. Genes 14 35627232
2022 CDK8 and CDK19 regulate intestinal differentiation and homeostasis via the chromatin remodeling complex SWI/SNF. The Journal of clinical investigation 14 36006697
2019 CDK11 Loss Induces Cell Cycle Dysfunction and Death of BRAF and NRAS Melanoma Cells. Pharmaceuticals (Basel, Switzerland) 14 30987032
2020 CDK11 negatively regulates Wnt/β-catenin signaling in the endosomal compartment by affecting microtubule stability. Cancer biology & medicine 13 32587772
2019 Transcriptional activation of CBFβ by CDK11p110 is necessary to promote osteosarcoma cell proliferation. Cell communication and signaling : CCS 13 31610798
2022 CDK8 and CDK19 act redundantly to control the CFTR pathway in the intestinal epithelium. EMBO reports 11 36545778
2020 Sexual cell cycle initiation is regulated by CDK19 and CYC9 in Tetrahymena thermophila. Journal of cell science 11 32041901
2010 Cyclin D3/CDK11(p58) complex involved in Schwann cells proliferation repression caused by lipopolysaccharide. Inflammation 11 20066559
2019 CDK11p58-cyclin L1β regulates abscission site assembly. The Journal of biological chemistry 10 31653703
2024 CD24 induced cellular quiescence-like state and chemoresistance in ovarian cancer cells via miR-130a/301a-dependent CDK19 downregulation. Cell death discovery 9 38360723
2023 Evodiamine inhibits malignant progression of ovarian cancer cells by regulating lncRNA-NEAT1/miR-152-3p/CDK19 axis. Chemical biology & drug design 9 36892495
2023 CDK11 facilitates centromeric transcription to maintain centromeric cohesion during mitosis. Molecular biology of the cell 9 38019613
2020 A cyclin-dependent kinase, CDK11/p58, represses cap-dependent translation during mitosis. Cellular and molecular life sciences : CMLS 9 32030451
2013 LPS-stimulating astrocyte-conditioned medium causes neuronal apoptosis via increasing CDK11(p58) expression in PC12 cells through downregulating AKT pathway. Cellular and molecular neurobiology 9 23703121
2023 PET imaging of new target CDK19 in prostate cancer. European journal of nuclear medicine and molecular imaging 8 37278941
2020 CDK19 as a Potential HPV-Independent Biomarker for Recurrent Disease in HNSCC. International journal of molecular sciences 8 32752128
2011 CDK11(p58) promotes rat astrocyte inflammatory response via activating p38 and JNK pathways induced by lipopolysaccharide. Neurochemical research 8 22120654
2020 ISOC1 promotes the proliferation of gastric cancer cells by positively regulating CDK19. European review for medical and pharmacological sciences 7 33275227
2022 Mitochondrial ribosomal small subunit (MRPS) MRPS23 protein-protein interaction reveals phosphorylation by CDK11-p58 affecting cell proliferation and knockdown of MRPS23 sensitizes breast cancer cells to CDK1 inhibitors. Molecular biology reports 6 35962848
2021 CDK19 as a diagnostic marker for high-grade prostatic intraepithelial neoplasia. Human pathology 6 34314763
2024 Novel CDK19-Targeted Radiotracers: A Potential Design Strategy to Improve the Pharmacokinetics and Tumor Uptake. Journal of medicinal chemistry 5 38570733
2021 A novel variant of CDK19 causes a severe neurodevelopmental disorder with infantile spasms. Cold Spring Harbor molecular case studies 5 33568421
2005 Diversification of CDK11 transcripts during chicken testis development and regression. Molecular reproduction and development 5 16094671
2025 On-target toxicity limits the efficacy of CDK11 inhibition against cancers with 1p36 deletions. bioRxiv : the preprint server for biology 4 40766692
2025 Cyclin-dependent kinase (CDK) 8 and its paralog CDK19 develop group 2 innate lymphoid cell-related lung fibrosis by activating STAT5. Journal of immunology (Baltimore, Md. : 1950) 3 40795210
2025 A CDK11-dependent RNA polymerase II pause-checkpoint precedes CDK9-mediated transition to transcriptional elongation. Molecular cell 2 40858114
2025 CDK7-CDK11 axis in spliceosome regulation and pre-mRNA splicing. Nucleic acids research 2 41428738
2019 CDK11 safeguards the identity of human embryonic stem cells via fine-tuning signaling pathways. Journal of cellular physiology 2 31612516
2026 CDK8 and CDK19 Mediator kinases are required for hepatitis delta virus replication. Hepatology (Baltimore, Md.) 1 41665877
2025 CDK11 inhibition induces cytoplasmic p21WAF1 splice variant by p53 stabilisation and SF3B1 inactivation. Molecular oncology 1 41105927
2025 Reprogramming the GRHL2-CDK19 axis by gene therapy alleviates prostate aging. Nature aging 1 41266629
2021 CDK11 Promotes Cytokine-Induced Apoptosis in Pancreatic Beta Cells Independently of Glucose Concentration and Is Regulated by Inflammation in the NOD Mouse Model. Frontiers in immunology 1 33664748
2019 Correction to: Transcriptional activation of CBFβ by CDK11p110 is necessary to promote osteosarcoma cell proliferation. Cell communication and signaling : CCS 1 31665012
2026 Uncovering functional insights into human pathogenic variants in CDK19 using Drosophila models. Human molecular genetics 0 41251503
2026 Romaciclib, a CDK8/CDK19 inhibitor, can overcome venetoclax resistance through a combinatorial strategy. bioRxiv : the preprint server for biology 0 41446261
2026 CDK8/CDK19 inhibition restores T-cell homeostasis in primary immune thrombocytopenia. Blood 0 41770851
2026 In Silico-Enabled Discovery and Development of Potent and Selective CDK11 Inhibitors. ChemMedChem 0 41886307
2026 Phosphorylation of SF3B1 by CDK11 orchestrates spliceosome activation via SNIP1-dependent RES complex recruitment. Nature communications 0 41904131
2026 Cryo-EM structures of the CDK11-cyclin L-SAP30BP complex reveal mechanisms of CDK11 regulation. Nature communications 0 42034640
2025 Synthesis and Imaging of Novel CDK19-Targeted Tracers Incorporating an Albumin-Binding Moiety. Journal of labelled compounds & radiopharmaceuticals 0 40077993
2025 Optimized CDK19 PET Tracers: Spirocyclic-Driven Design and Prostate Cancer Imaging. Journal of medicinal chemistry 0 40679172
2025 CDK11 Mediates Autophagy to Promote Breast Cancer Cell Proliferation and Migration by Regulating BCL-2. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 40853089
2025 CDK11 Promotes Paclitaxel Resistance in Cervical Cancer by Regulating LATS1-Mediated Hippo Signaling Pathway Through Phosphorylation of NF2. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 41074747
2025 Transcriptional cyclin-dependent kinases Cdk8 and Cdk19 are required for normal macrophage differentiation. Cell cycle (Georgetown, Tex.) 0 41123539
2025 NUDT21-mediated Alternative Polyadenylation of CDK19 Reprograms Cholesterol Biosynthesis to Drive Colorectal Cancer Progression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41255211
2025 CDK11 activates CDK12 to trigger the elongation of RNA Polymerase II. bioRxiv : the preprint server for biology 0 41377501
2021 Stability of Imprinting and Differentiation Capacity in Naïve Human Cells Induced by Chemical Inhibition of CDK8 and CDK19. Cells 0 33921436