CDK8

Oncogene
Cyclin-dependent kinase 8 UniProt accession P49336

Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional pre-initiation complex with RNA polymerase II and the general transcription factors.

Phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex. Phosphorylates CCNH leading to down-regulation of the TFIIH complex and transcriptional repression. Recruited through interaction with MAML1 to hyperphosphorylate the intracellular domain of NOTCH, leading to its degradation

Source: UniProt

Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation.

Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. The cylin/CDK pair formed by CCNC/CDK8 also associates with the large subunit of RNA polymerase II. Interacts with CTNNB1, GLI3 and MAML1

Source: UniProt
Nucleus
Source: UniProt
  • Intellectual developmental disorder with hypotonia and behavioral abnormalities (IDDHBA)

    An autosomal dominant neurodevelopmental disorder with onset in infancy. IDDHBA is characterized by hypotonia, global developmental delay, learning disability, and behavioral abnormalities, such as autistic features and attention deficit-hyperactivity disorder. Additional variable features may include non-specific facial dysmorphism, congenital heart defects, ocular anomalies, and poor feeding.

Source: UniProt
  • PPARA activates gene expression
  • NOTCH1 Intracellular Domain Regulates Transcription
  • Generic Transcription Pathway
  • SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
  • Constitutive Signaling by NOTCH1 PEST Domain Mutants
  • Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
  • Transcriptional regulation of white adipocyte differentiation
  • RSV-host interactions
  • MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis
Source: Reactome via UniProt

Mutations

Cancer Type Mutation Percentage
Central Nervous System Astrocytoma Grade Iv 0.38%
Lung Adenocarcinoma 1.05%
Lung Small Cell Carcinoma 0.59%
Lung Squamous Cell Carcinoma 1.50%
Oesophagus Adenocarcinoma 1.24%
Oesophagus Squamous Cell Carcinoma 0.59%
Pancreas Ductal Carcinoma 0.33%

Synthetic Lethal Network

Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to CDK8, aggregated across our SSL data sources. Click any partner node to view that gene’s page.

Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.

BioGRID SLOrth SynLethDB MexDrugs Multi-source
Sources: BioGRID, SLOrth, SynLethDB, MexDrugs

Clinical Trials

Total Trials Found: 2

NCT ID Condition Brief Title Phase Status
NCT04021368 Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome RVU120 in Patients With Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome PHASE1 UNKNOWN
NCT06243458 Low Risk Myelodysplastic Syndromes RVU120 for Treatment of Anemia in Patients With Lower-risk Myelodysplastic Neoplasms PHASE2 ACTIVE_NOT_RECRUITING