Cyclin-dependent kinase 8

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Cyclin-dependent kinase 8
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols CDK8 ; K35
External IDs OMIM603184 MGI1196224 HomoloGene55565 ChEMBL: 5719 GeneCards: CDK8 Gene
EC number,
RNA expression pattern
PBB GE CDK8 204831 at tn.png
More reference expression data
Species Human Mouse
Entrez 1024 264064
Ensembl ENSG00000132964 ENSMUSG00000029635
UniProt P49336 Q8R3L8
RefSeq (mRNA) NM_001260 NM_153599
RefSeq (protein) NP_001251 NP_705827
Location (UCSC) Chr 13:
26.25 – 26.41 Mb
Chr 5:
146.23 – 146.3 Mb
PubMed search [1] [2]

Cell division protein kinase 8 is an enzyme that in humans is encoded by the CDK8 gene.[1][2]


The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK8 and cyclin C associate with the Mediator complex and regulate transcription by currently not well-understood mechanisms. Only a few direct substrates of CDK8 have been identified and validated by independent studies. One such CDK8 substrate is STAT1 S727.[3]

Role in Cancer/Drug Target[edit]

The natural product cortistatin A is a highly potent and selective inhibitor of CDK8 and its highly similar homolog CDK19.[4] Inhibition of CDK8 and CDK19 with cortistatin A potently suppresses growth AML cells and has significant anti-leukemic activity in vivo. Inhibition of CDK8 and CDK19 is a new therapeutic approach to AML. Inhibition of CDK8/CDK19 in AML causes selective and disproportionate up regulation of super-enhancer-associated genes including the cell identity genes CEBPA and IRF8. These effects contribute to the anti-leukemic activity of cortistatin A and reveal that CDK8/19 restrain heightened activation of specific super-enhancer-associated genes in AML.

See also Protein kinase domain to view the more general properties of kinases.


Cyclin-dependent kinase 8 has been shown to interact with:


  1. ^ a b Tassan JP, Jaquenoud M, Léopold P, Schultz SJ, Nigg EA (Sep 1995). "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proceedings of the National Academy of Sciences of the United States of America 92 (19): 8871–5. doi:10.1073/pnas.92.19.8871. PMC 41069. PMID 7568034. 
  2. ^ "Entrez Gene: CDK8 cyclin-dependent kinase 8". 
  3. ^ Bancerek, Joanna; Poss, Zachary C.; Steinparzer, Iris; Sedlyarov, Vitaly; Pfaffenwimmer, Thaddäus; Mikulic, Ivana; Dölken, Lars; Strobl, Birgit; Müller, Mathias. "CDK8 Kinase Phosphorylates Transcription Factor STAT1 to Selectively Regulate the Interferon Response". Immunity 38 (2): 250–262. doi:10.1016/j.immuni.2012.10.017. ISSN 1074-7613. PMC 3580287. PMID 23352233. 
  4. ^ Pelish, Henry E.; Liau, Brian B.; Nitulescu, Ioana I.; Tangpeerachaikul, Anupong; Poss, Zachary C.; Silva, Diogo H. Da; Caruso, Brittany T.; Arefolov, Alexander; Fadeyi, Olugbeminiyi. "Mediator kinase inhibition further activates super-enhancer-associated genes in AML". Nature 526 (7572): 273–276. doi:10.1038/nature14904. 
  5. ^ a b c d e f g h i Kang YK, Guermah M, Yuan CX, Roeder RG (Mar 2002). "The TRAP/Mediator coactivator complex interacts directly with estrogen receptors alpha and beta through the TRAP220 subunit and directly enhances estrogen receptor function in vitro". Proceedings of the National Academy of Sciences of the United States of America 99 (5): 2642–7. doi:10.1073/pnas.261715899. PMC 122401. PMID 11867769. 
  6. ^ a b c d Wang G, Cantin GT, Stevens JL, Berk AJ (Jul 2001). "Characterization of mediator complexes from HeLa cell nuclear extract". Molecular and Cellular Biology 21 (14): 4604–13. doi:10.1128/MCB.21.14.4604-4613.2001. PMC 87123. PMID 11416138. 
  7. ^ a b c d e Cho H, Orphanides G, Sun X, Yang XJ, Ogryzko V, Lees E, Nakatani Y, Reinberg D (Sep 1998). "A human RNA polymerase II complex containing factors that modify chromatin structure". Molecular and Cellular Biology 18 (9): 5355–63. PMC 109120. PMID 9710619. 
  8. ^ Zhang Y, Iratni R, Erdjument-Bromage H, Tempst P, Reinberg D (May 1997). "Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex". Cell 89 (3): 357–64. doi:10.1016/s0092-8674(00)80216-0. PMID 9150135. 
  9. ^ a b c d e f g h Ito M, Yuan CX, Malik S, Gu W, Fondell JD, Yamamura S, Fu ZY, Zhang X, Qin J, Roeder RG (Mar 1999). "Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators". Molecular Cell 3 (3): 361–70. doi:10.1016/s1097-2765(00)80463-3. PMID 10198638. 
  10. ^ Suñé C, Hayashi T, Liu Y, Lane WS, Young RA, Garcia-Blanco MA (Oct 1997). "CA150, a nuclear protein associated with the RNA polymerase II holoenzyme, is involved in Tat-activated human immunodeficiency virus type 1 transcription". Molecular and Cellular Biology 17 (10): 6029–39. PMC 232452. PMID 9315662. 
  11. ^ Sato S, Tomomori-Sato C, Parmely TJ, Florens L, Zybailov B, Swanson SK, Banks CA, Jin J, Cai Y, Washburn MP, Conaway JW, Conaway RC (Jun 2004). "A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology". Molecular Cell 14 (5): 685–91. doi:10.1016/j.molcel.2004.05.006. PMID 15175163. 
  12. ^ Yang F, DeBeaumont R, Zhou S, Näär AM (Feb 2004). "The activator-recruited cofactor/Mediator coactivator subunit ARC92 is a functionally important target of the VP16 transcriptional activator". Proceedings of the National Academy of Sciences of the United States of America 101 (8): 2339–44. doi:10.1073/pnas.0308676100. PMC 356952. PMID 14983011. 

Further reading[edit]

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