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Gene Review

CDK8  -  cyclin-dependent kinase 8

Homo sapiens

Synonyms: Cell division protein kinase 8, Cyclin-dependent kinase 8, K35, Mediator complex subunit CDK8, Mediator of RNA polymerase II transcription subunit CDK8, ...
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Disease relevance of CDK8


High impact information on CDK8


Biological context of CDK8


Anatomical context of CDK8

  • To further understand the structural and functional diversity of these complexes we established three HeLa cell lines each expressing one of three epitope-tagged human TRAP/Mediator subunits, MED6, MED7, and CDK8 and isolated the complexes in which these subunits were contained by affinity and HPLC-gel filtration chromatography [10].
  • Colocalization of cyclin C and its preferred binding partner, Cdk8, was only observed in astrocytes but not in neurons [11].

Associations of CDK8 with chemical compounds

  • Immunoprecipitation of the approximately 2-MDa fraction with anti-Cdk8 antibody indicated that at least two classes of Mediator complexes occur, one containing CDK8 and cyclin C and one lacking this CDK-cyclin pair [12].
  • The composition of these complexes was analyzed by centrifugation over sucrose gradients, by gel filtration, by RIA with either IgG Sepharose or K35 Sepharose and by double-labeling studies [13].
  • In the absence of the Zn(2+) ion, K6 and K35 on the top of the PC molecule also interact with cyt f [14].
  • E/E35 contains only glutamic acid at both e and g positions; K/K35, only lysine, E/E35 and K/K35 were designed to form a stable coiled coil heterodimer when combined at neutral pH [15].
  • RESULTS: OMP analysis revealed that cefoxitin and ceftazidime resistance was mediated by loss of a porin Omp K35 in the isolates of K.pneumoniae and E.coli [16].

Physical interactions of CDK8

  • We have identified at least two distinct cyclin C/CDK8 containing complexes within the cell, a larger complex over 500 kD in size, that also contains the largest subunit of RNA polymerase II, and a smaller 170 kD species [17].

Other interactions of CDK8

  • Cyclin C/CDK8 is a novel CTD kinase associated with RNA polymerase II [17].
  • Additionally, the motifs showed CDK8 to be lower relative to ICAM1, and ANXA5 to be relatively high by itself in node positive tumors [18].
  • We provide in vitro and in vivo evidence that VP16 activates transcription through a specific MED25-associated Mediator, which is deficient in CDK8 [19].
  • Kinases responsible for such CTD phosphorylation that are associated with RNA polymerase II at distinct steps of transcription, such as cdk7 and cdk8, also phosphorylate some other components of the transcription machinery in a regulatory manner [20].

Analytical, diagnostic and therapeutic context of CDK8

  • We use electron microscopy and single-particle reconstruction to demonstrate that the Cdk8 module forms a distinct structural entity that binds to the head and middle region of Mediator, thereby sterically blocking interactions with pol II [7].


  1. Targeting of CDK8 to a promoter-proximal RNA element demonstrates catalysis-dependent activation of gene expression. Gold, M.O., Rice, A.P. Nucleic Acids Res. (1998) [Pubmed]
  2. Recruitment of TFIIH to the HIV LTR is a rate-limiting step in the emergence of HIV from latency. Kim, Y.K., Bourgeois, C.F., Pearson, R., Tyagi, M., West, M.J., Wong, J., Wu, S.Y., Chiang, C.M., Karn, J. EMBO J. (2006) [Pubmed]
  3. Regulation of the oxidative stress response through Slt2p-dependent destruction of cyclin C in Saccharomyces cerevisiae. Krasley, E., Cooper, K.F., Mallory, M.J., Dunbrack, R., Strich, R. Genetics (2006) [Pubmed]
  4. Genome-wide cDNA microarray screening of genes related to survival in patients after curative resection of non-small cell lung cancer. Oshita, F., Sekiyama, A., Ito, H., Kameda, Y., Miyagi, Y. Oncol. Rep. (2006) [Pubmed]
  5. TFIIH is negatively regulated by cdk8-containing mediator complexes. Akoulitchev, S., Chuikov, S., Reinberg, D. Nature (2000) [Pubmed]
  6. Genome-wide location of the coactivator mediator: Binding without activation and transient Cdk8 interaction on DNA. Andrau, J.C., van de Pasch, L., Lijnzaad, P., Bijma, T., Koerkamp, M.G., van de Peppel, J., Werner, M., Holstege, F.C. Mol. Cell (2006) [Pubmed]
  7. The cyclin-dependent kinase 8 module sterically blocks Mediator interactions with RNA polymerase II. Elmlund, H., Baraznenok, V., Lindahl, M., Samuelsen, C.O., Koeck, P.J., Holmberg, S., Hebert, H., Gustafsson, C.M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  8. Three RNA polymerase II carboxyl-terminal domain kinases display distinct substrate preferences. Ramanathan, Y., Rajpara, S.M., Reza, S.M., Lees, E., Shuman, S., Mathews, M.B., Pe'ery, T. J. Biol. Chem. (2001) [Pubmed]
  9. Functional cooperation of cyclin C and c-Myc in mediating homotypic cell adhesion via very late antigen-4 activation and vascular cell adhesion molecule-1 induction. Liu, Z.J., Tanaka, Y., Mine, S., Morinobu, A., Yagita, H., Okumura, K., Taniguchi, T., Yamamura, H., Minami, Y. Blood (1998) [Pubmed]
  10. A kinase subunit of the human mediator complex, CDK8, positively regulates transcriptional activation. Furumoto, T., Tanaka, A., Ito, M., Malik, S., Hirose, Y., Hanaoka, F., Ohkuma, Y. Genes Cells (2007) [Pubmed]
  11. Cyclin C expression is involved in the pathogenesis of Alzheimer's disease. Ueberham, U., Hessel, A., Arendt, T. Neurobiol. Aging (2003) [Pubmed]
  12. Characterization of mediator complexes from HeLa cell nuclear extract. Wang, G., Cantin, G.T., Stevens, J.L., Berk, A.J. Mol. Cell. Biol. (2001) [Pubmed]
  13. Binding characteristics of dimeric IgG subclass complexes to human neutrophils. Huizinga, T.W., Kerst, M., Nuyens, J.H., Vlug, A., von dem Borne, A.E., Roos, D., Tetteroo, P.A. J. Immunol. (1989) [Pubmed]
  14. A Brownian dynamics study of the interaction of Phormidium laminosum plastocyanin with Phormidium laminosum cytochrome f. Gross, E.L. Biophys. J. (2004) [Pubmed]
  15. Controlled formation of model homo- and heterodimer coiled coil polypeptides. Graddis, T.J., Myszka, D.G., Chaiken, I.M. Biochemistry (1993) [Pubmed]
  16. Cefoxitin resistance mediated by loss of a porin in clinical strains of Klebsiella pneumoniae and Escherichia coli. Ananthan, S., Subha, A. Indian journal of medical microbiology. (2005) [Pubmed]
  17. Cyclin C/CDK8 is a novel CTD kinase associated with RNA polymerase II. Rickert, P., Seghezzi, W., Shanahan, F., Cho, H., Lees, E. Oncogene (1996) [Pubmed]
  18. The use of genetic programming in the analysis of quantitative gene expression profiles for identification of nodal status in bladder cancer. Mitra, A.P., Almal, A.A., George, B., Fry, D.W., Lenehan, P.F., Pagliarulo, V., Cote, R.J., Datar, R.H., Worzel, W.P. BMC Cancer (2006) [Pubmed]
  19. The VP16 Activation Domain Establishes an Active Mediator Lacking CDK8 in Vivo. Uhlmann, T., Boeing, S., Lehmbacher, M., Meisterernst, M. J. Biol. Chem. (2007) [Pubmed]
  20. Phosphorylation in transcription: the CTD and more. Riedl, T., Egly, J.M. Gene Expr. (2000) [Pubmed]
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