Property Summary

NCBI Gene PubMed Count 73
PubMed Score 102.73
PubTator Score 72.98

Knowledge Summary

Patent (13,721)

Expression

  Differential Expression (11)

Disease log2 FC p
psoriasis -1.300 3.8e-04
osteosarcoma -4.264 1.1e-09
group 4 medulloblastoma 1.600 2.9e-03
medulloblastoma, large-cell 1.700 2.4e-04
adrenocortical carcinoma 1.095 4.4e-02
intraductal papillary-mucinous neoplasm ... 1.200 2.9e-02
lung cancer 2.400 1.7e-03
subependymal giant cell astrocytoma -1.874 1.2e-03
ovarian cancer -1.100 1.7e-03
Breast cancer 1.300 1.0e-03
pituitary cancer 1.100 1.3e-02

MLP Assay (1)

AID Type Active / Inconclusive / Inactive Description
1982 other 0 / 0 / 0 Kinase inhibition selectivity assay for compound SID-48409448

Gene RIF (46)

PMID Text
26496706 Collectively, our results implicate Ste12 and Tec1 as general and important contributors to the Cdk8, RNAPII-CTD regulatory circuitry as it relates to the maintenance of genome integrity
26452386 the expression of CDK8 and its interactive genes has a profound impact on the response to adjuvant therapy in breast cancer in accordance with the role of CDK8 in chemotherapy-induced tumor-supporting paracrine activities--{REVIEW}
26416749 Mediator-associated kinases CDK8 and CDK19 restrain increased activation of key super-enhancer-associated genes in acute myeloid leukaemia (AML) cells
26349978 our data provided evidence that CDK-8 played a significant role in colon cancer hepatic metastasis by regulating the Wnt/beta-catenin signal pathway
26286725 miR-101 is a potent tumor repressor that directly represses CDK8 expression
26182352 Data suggest that MED13, MED12, CDK8 and cyclin C (CycC) comprise a four-subunit "kinase" module of the Mediator complex that functions as a major ingress of oncogenic and developmental signaling/gene expression in humans. [REVIEW]
26042770 our results suggest that mTORC1 activation in NAFLD and insulin resistance results in down-regulation of the CDK8-CycC complex and elevation of lipogenic protein expression.
26006748 Current state of the art confirms that further development of CDK8 inhibitors will translate into targeted therapies in oncology
26002960 Data suggest that, during neurogenesis, Mediator complex cyclin-dependent kinases (CDK8, CDK19) interact directly with PRC2 (polycomb repressive complex 2) subunit EZH2 (enhancer of zeste homolog 2), as well as SUZ12 (suppressor of zeste 12 homolog).
25818643 The Skp2-mH2A1-CDK8 axis has a critical role in breast cancer development via dysregulation of the G2/M transition, polyploidy, cell growth dysregulation, and loss of tumor suppression.
25400821 Suggest that miR-107 plays a key role in cisplatin resistance by targeting the CDK8 protein in non small cell lung cancer cells.
24840924 A novel transcriptional repression mechanism of hMED18 mediated by hCDK8 and further a novel positive role of free CDK/cyclin module in transcriptional activation is described.
24754906 Cancer-mediated CDK8 point mutations (D173A and D189N) change the binding pattern of cdk8 to its partner, CycC.
24439911 Cdk8 is required for stress-induced Mdv1-Dnm1 interaction and mitochondrial fragmentation.
24427329 CDK8 plays an essential role in breast cancer progression
24139904 CDK8 regulates the transcription factors turnover, C-terminal domain phosphorylation, and regulates the activator or repressor functions. (Review)
24009531 Here, loss of CDK8 suppressed the reduced mRNA expression and RNAPII occupancy levels of CTD truncation mutants.
23827503 HIV-1 Tat interacts with the RNA polymerase II holoenzyme, which includes CDK8, during Tat-mediated transactivation of the HIV-1 LTR
23749998 CDK8 and CDK19, individually interact with PRMT5 and WDR77, and their interactions with PRMT5 cause transcriptional repression of C/EBPbeta target genes.
23746844 Study reports that HIF1A employs a specific variant of the Mediator complex to stimulate RNAPII elongation; the Mediator-associated kinase CDK8, but not the paralog CDK19, is required for induction of many HIF1A target genes.
23630251 analysis of the structure-kinetic relationship of the cyclin-dependent kinase 8 (CDK8)/cyclin C (CycC) complex
23563140 Authors found that interaction of the CDK8 kinase module with Mediator's middle module interferes with C-terminal domain-dependent RNAPII binding to a previously unknown middle-module CTD-binding site and with the holoenzyme formation process.
23454913 results show a reverse correlation between CDK8 levels and several key features of the endometrial cancer cells, including cell proliferation, migration and invasion as well as tumor formation in vivo
23352233 CDK8 is a key regulator of STAT1 and antiviral responses.
22945643 The phosphorylation of S375 by CDK8 regulates E2F1 ability to repress transcription of beta-catenin/TCF-dependent genes, as well as activation of E2F1-dependent genes.
22869755 Cyclin-dependent kinase 8 mediates chemotherapy-induced tumor-promoting paracrine activities
22379099 Retroviral cyclin enhances cyclin-dependent kinase-8 activity.
22345154 we identify a role for the CDK8 oncogene in regulating tumor differentiation and stem cell pluripotency
22117896 Microarrays identified target genes for each CDK, and we selected six genes: two target genes of CDK8, two target genes of CDK19 and two genes that were targets for both.
21806996 2.2-A crystal structure of CDK8/CycC in complex with sorafenib; the CDK8 activation loop appears not to be phosphorylated. Based on the structure, we discuss an alternate mode of CDK8 activation to the general CDK activation by T-loop phosphorylation
21344156 beta-catenin expression was suppressed by CDK8 interference in the gastric adenocarcinoma cell lines.
21179167 significant inverse correlation between mH2A and CDK8 expression levels exists in melanoma patient samples
21067790 The Walleye dermal sarcoma virus cyclin functions as a structural ortholog of cyclin C in spite of its limited amino acid sequence identity with C cyclins or with any known cyclins and activates Cdk8 and Cdk3.
20514474 CDK8 may identify a subset of colon cancer patients with poor prognosis.
20408451 plays a role in mechanisms of transcriptional regulation upon protein phosphorylation. (review)
20098423 The authors show, using a human tumor cell line, that CDK8 is a positive regulator of genes within the serum response network, including several members of the activator protein 1 and early growth response family of oncogenic transcription factors.
20083228 Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
19790197 Overexpression of CDK8 is associated with beta-catenin activation and colon cancer.
19240132 Med12 and Med13 are critical for human CDK8 subcomplex -dependent repression, whereas CDK8 kinase activity is not
19047373 Med12--but not Med13--is essential for activating the CDK8 kinase.
18794900 CDK8 kinase activity was necessary for beta-catenin-driven transformation and for expression of several beta-catenin transcriptional targets
18794899 by retaining RB1 and amplifying CDK8, colorectal tumour cells select conditions that collectively suppress E2F1 and enhance the activity of beta-catenin
18418385 Within T/G-Mediator, cdk8 phosphorylates serine-10 on histone H3, which in turn stimulates H3K14 acetylation by GCN5L within the complex.
17612495 RNA interference experiments demonstrate that CDK8 functions as a coactivator within the p53 transcriptional program.
17212659 CDK8 play positive roles in transcriptional activation.
9121429 HIV-1 Tat interacts with the RNA polymerase II holoenzyme, which includes CDK8, during Tat-mediated transactivation of the HIV-1 LTR

AA Sequence

MDYDFKVKLSSERERVEDLFEYEGCKVGRGTYGHVYKAKRKDGKDDKDYALKQIEGTGISMSACREIALL      1 - 70
RELKHPNVISLQKVFLSHADRKVWLLFDYAEHDLWHIIKFHRASKANKKPVQLPRGMVKSLLYQILDGIH     71 - 140
YLHANWVLHRDLKPANILVMGEGPERGRVKIADMGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARH    141 - 210
YTKAIDIWAIGCIFAELLTSEPIFHCRQEDIKTSNPYHHDQLDRIFNVMGFPADKDWEDIKKMPEHSTLM    211 - 280
KDFRRNTYTNCSLIKYMEKHKVKPDSKAFHLLQKLLTMDPIKRITSEQAMQDPYFLEDPLPTSDVFAGCQ    281 - 350
IPYPKREFLTEEEPDDKGDKKNQQQQQGNNHTNGTGHPGNQDSSHTQGPPLKKVRVVPPTTTSGGLIMTS    351 - 420
DYQRSNPHAAYPNPGPSTSQPQSSMGYSATSQQPPQYSHQTHRY                              421 - 464
//

Text Mined References (79)

PMID Year Title
26678610 2016 Transcriptional kinases: Less is more (or less).
26496706 2015 The RNAPII-CTD Maintains Genome Integrity through Inhibition of Retrotransposon Gene Expression and Transposition.
26452386 2015 Expression of CDK8 and CDK8-interacting Genes as Potential Biomarkers in Breast Cancer.
26416749 2015 Mediator kinase inhibition further activates super-enhancer-associated genes in AML.
26349978 2015 Downregulation of CDK-8 inhibits colon cancer hepatic metastasis by regulating Wnt/?-catenin pathway.
26286725 2015 MicroRNA-101 is a potential prognostic indicator of laryngeal squamous cell carcinoma and modulates CDK8.
26182352 2015 Mediator kinase module and human tumorigenesis.
26042770 2015 mTORC1 Down-Regulates Cyclin-Dependent Kinase 8 (CDK8) and Cyclin C (CycC).
26006748 2015 CDK8 kinase--An emerging target in targeted cancer therapy.
26002960 2015 Mediator complex cooperatively regulates transcription of retinoic acid target genes with Polycomb Repressive Complex 2 during neuronal differentiation.
25818643 2015 Skp2-macroH2A1-CDK8 axis orchestrates G2/M transition and tumorigenesis.
25416956 2014 A proteome-scale map of the human interactome network.
25400821 2014 miR-107 regulates cisplatin chemosensitivity of A549 non small cell lung cancer cell line by targeting cyclin dependent kinase 8.
24840924 2014 Mediator MED18 subunit plays a negative role in transcription via the CDK/cyclin module.
24811271 2014 Genome-wide SNP associations with rubella-specific cytokine responses in measles-mumps-rubella vaccine recipients.
24754906 2014 All-atomic molecular dynamic studies of human CDK8: insight into the A-loop, point mutations and binding with its partner CycC.
24439911 2014 Stress-induced nuclear-to-cytoplasmic translocation of cyclin C promotes mitochondrial fission in yeast.
24427329 2014 siRNA-mediated silencing of CDK8 inhibits proliferation and growth in breast cancer cells.
24139904 2014 The two faces of Cdk8, a positive/negative regulator of transcription.
24009531 2013 High-throughput genetic and gene expression analysis of the RNAPII-CTD reveals unexpected connections to SRB10/CDK8.
23749998 2013 Mediator complex recruits epigenetic regulators via its two cyclin-dependent kinase subunits to repress transcription of immune response genes.
23746844 2013 HIF1A employs CDK8-mediator to stimulate RNAPII elongation in response to hypoxia.
23630251 2013 Structure-kinetic relationship study of CDK8/CycC specific compounds.
23602568 2013 The protein interaction landscape of the human CMGC kinase group.
23563140 2013 A conserved Mediator-CDK8 kinase module association regulates Mediator-RNA polymerase II interaction.
23454913 2013 Tumor-suppressive effects of CDK8 in endometrial cancer cells.
23352233 2013 CDK8 kinase phosphorylates transcription factor STAT1 to selectively regulate the interferon response.
22945643 2013 CDK8 regulates E2F1 transcriptional activity through S375 phosphorylation.
22869755 2012 Cyclin-dependent kinase 8 mediates chemotherapy-induced tumor-promoting paracrine activities.
22379099 2012 Retroviral cyclin enhances cyclin-dependent kinase-8 activity.
22345154 2012 CDK8 maintains tumor dedifferentiation and embryonic stem cell pluripotency.
22117896 2011 Identification of target genes for the CDK subunits of the Mediator complex.
21806996 2011 The structure of CDK8/CycC implicates specificity in the CDK/cyclin family and reveals interaction with a deep pocket binder.
21344156 2011 Roles of cyclin-dependent kinase 8 and ?-catenin in the oncogenesis and progression of gastric adenocarcinoma.
21179167 2010 The histone variant macroH2A suppresses melanoma progression through regulation of CDK8.
21067790 2011 The retroviral cyclin of walleye dermal sarcoma virus binds cyclin-dependent kinases 3 and 8.
20514474 2010 Role of CDK8 and beta-catenin in colorectal adenocarcinoma.
20408451 2010 [Mechanisms of transcriptional regulation upon protein phosphorylation by mediator complexes].
20098423 2010 CDK8 is a positive regulator of transcriptional elongation within the serum response network.
20083228 2010 Genome-wide analysis of chromosomal alterations in patients with esophageal squamous cell carcinoma exposed to tobacco and betel quid from high-risk area in India.
19914168 2009 Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-beta pathways.
19790197 2010 CDK8 expression in 470 colorectal cancers in relation to beta-catenin activation, other molecular alterations and patient survival.
19369195 2009 Large-scale proteomics analysis of the human kinome.
19240132 2009 The human CDK8 subcomplex is a molecular switch that controls Mediator coactivator function.
19047373 2009 The human CDK8 subcomplex is a histone kinase that requires Med12 for activity and can function independently of mediator.
18794900 2008 CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity.
18794899 2008 E2F1 represses beta-catenin transcription and is antagonized by both pRB and CDK8.
18418385 2008 Cooperative activity of cdk8 and GCN5L within Mediator directs tandem phosphoacetylation of histone H3.
17612495 2007 CDK8 is a stimulus-specific positive coregulator of p53 target genes.
17344846 2007 Patterns of somatic mutation in human cancer genomes.
17212659 2007 A kinase subunit of the human mediator complex, CDK8, positively regulates transcriptional activation.
17000779 2006 Mediator modulates Gli3-dependent Sonic hedgehog signaling.
16109376 2005 The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription.
15989967 2005 MED1/TRAP220 exists predominantly in a TRAP/ Mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription.
15546612 2004 Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15175163 2004 A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology.
15057823 2004 The DNA sequence and analysis of human chromosome 13.
14983011 2004 The activator-recruited cofactor/Mediator coactivator subunit ARC92 is a functionally important target of the VP16 transcriptional activator.
14638676 2004 A mammalian mediator subunit that shares properties with Saccharomyces cerevisiae mediator subunit Cse2.
12584197 2003 Identification of mammalian Mediator subunits with similarities to yeast Mediator subunits Srb5, Srb6, Med11, and Rox3.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12145330 2002 Reproductive cycle regulation of nuclear import, euchromatic localization, and association with components of Pol II mediator of a mammalian double-bromodomain protein.
12007796 2002 Molecular cloning and characterisation of p15(CDK-BP), a novel CDK-binding protein.
11441538 1999 Genomics of the human genes encoding four TAFII subunits of TFIID, the three subunits of TFIIA, as well as CDK8 and SURB7.
11416138 2001 Characterization of mediator complexes from HeLa cell nuclear extract.
11278802 2001 Three RNA polymerase II carboxyl-terminal domain kinases display distinct substrate preferences.
10993082 2000 TFIIH is negatively regulated by cdk8-containing mediator complexes.
10235266 1999 Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex.
10198638 1999 Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators.
10024883 1999 A novel human SRB/MED-containing cofactor complex, SMCC, involved in transcription regulation.
10023686 1999 Cyclin C/CDK8 and cyclin H/CDK7/p36 are biochemically distinct CTD kinases.
9734358 1998 NAT, a human complex containing Srb polypeptides that functions as a negative regulator of activated transcription.
9710619 1998 A human RNA polymerase II complex containing factors that modify chromatin structure.
9443979 1998 Factors associated with the mammalian RNA polymerase II holoenzyme.
9121429 1997 The human immunodeficiency virus transactivator Tat interacts with the RNA polymerase II holoenzyme.
8700522 1996 Cyclin C/CDK8 is a novel CTD kinase associated with RNA polymerase II.
8274451 1993 Identification of 21 novel human protein kinases, including 3 members of a family related to the cell cycle regulator nimA of Aspergillus nidulans.
7568034 1995 Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C.