Cdk8

Summary

Gene Symbol: Cdk8
Description: cyclin-dependent kinase 8
Alias: cyclin-dependent kinase 8, cell division protein kinase 8, mediator complex subunit CDK8, mediator of RNA polymerase II transcription subunit CDK8
Species: mouse
Products:     Cdk8

Top Publications

  1. Alarcon C, Zaromytidou A, Xi Q, Gao S, Yu J, Fujisawa S, et al. Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-beta pathways. Cell. 2009;139:757-69 pubmed publisher
    ..receptor-activated Smads form transcriptional complexes, they are phosphorylated at an interdomain linker region by CDK8 and CDK9, which are components of transcriptional mediator and elongation complexes...
  2. Bancerek J, Poss Z, Steinparzer I, Sedlyarov V, Pfaffenwimmer T, Mikulic I, et al. CDK8 kinase phosphorylates transcription factor STAT1 to selectively regulate the interferon response. Immunity. 2013;38:250-62 pubmed publisher
    ..Here, we show that the cyclin-dependent kinase 8 (CDK8) module of the Mediator complex phosphorylated regulatory sites within the TADs of STAT1, STAT3, and STAT5, ..
  3. Wang G, Balamotis M, Stevens J, Yamaguchi Y, Handa H, Berk A. Mediator requirement for both recruitment and postrecruitment steps in transcription initiation. Mol Cell. 2005;17:683-94 pubmed
    ..These results indicate that an interaction with MED23 stimulates initiation by promoter bound Pol II in addition to Pol II and GTF recruitment. ..
  4. Westerling T, Kuuluvainen E, Makela T. Cdk8 is essential for preimplantation mouse development. Mol Cell Biol. 2007;27:6177-82 pubmed
    The Cdk8 kinase and associated proteins form a nonessential transcriptional repressor module of the Mediator in the budding yeast Saccharomyces cerevisiae...
  5. McCleland M, Soukup T, Liu S, Esensten J, De Sousa E Melo F, Yaylaoglu M, et al. Cdk8 deletion in the Apc(Min) murine tumour model represses EZH2 activity and accelerates tumourigenesis. J Pathol. 2015;237:508-19 pubmed publisher
    b>CDK8 is a dissociable kinase module of the Mediator complex and has been shown to play an important role in transcriptional regulation in organisms as diverse as yeast and humans...
  6. Kapoor A, Goldberg M, Cumberland L, Ratnakumar K, Segura M, Emanuel P, et al. The histone variant macroH2A suppresses melanoma progression through regulation of CDK8. Nature. 2010;468:1105-9 pubmed publisher
    ..function of mH2A loss is mediated, at least in part, through direct transcriptional upregulation of CDK8. Suppression of CDK8, a colorectal cancer oncogene, inhibits proliferation of melanoma cells, and knockdown of CDK8 ..
  7. Xu D, Li C, Zhang X, Gong Z, Chan C, Lee S, et al. Skp2-macroH2A1-CDK8 axis orchestrates G2/M transition and tumorigenesis. Nat Commun. 2015;6:6641 pubmed publisher
    ..Here we identify the Skp2-macroH2A1 (mH2A1)-cyclin-dependent kinase 8 (CDK8) axis as a critical pathway for these processes, and deregulation of this pathway is associated with human breast ..
  8. Feng D, Youn D, Zhao X, Gao Y, Quinn W, Xiaoli A, et al. mTORC1 Down-Regulates Cyclin-Dependent Kinase 8 (CDK8) and Cyclin C (CycC). PLoS ONE. 2015;10:e0126240 pubmed publisher
    ..Recently, we show that CDK8 functions to suppress de novo lipogenesis...
  9. Johannessen L, Sundberg T, O Connell D, Kolde R, Berstler J, Billings K, et al. Small-molecule studies identify CDK8 as a regulator of IL-10 in myeloid cells. Nat Chem Biol. 2017;13:1102-1108 pubmed publisher
    ..studies using a prioritized hit from the screen, BRD6989, identified the Mediator-associated kinase CDK8, and its paralog CDK19, as negative regulators of IL-10 production during innate immune activation...

More Information

Publications17

  1. Aranda Orgilles B, Saldaña Meyer R, Wang E, Trompouki E, Fassl A, Lau S, et al. MED12 Regulates HSC-Specific Enhancers Independently of Mediator Kinase Activity to Control Hematopoiesis. Cell Stem Cell. 2016;19:784-799 pubmed publisher
    ..As MED12 mutations have been described recently in blood malignancies, alterations in MED12-dependent enhancer regulation may control both physiological and malignant hematopoiesis. ..
  2. Persaud S, Huang W, Park S, Wei L. Gene repressive activity of RIP140 through direct interaction with CDK8. Mol Endocrinol. 2011;25:1689-98 pubmed publisher
    ..of lysine acetylation-mimetic RIP140, which elicits a stronger repressive effect and more efficiently recruits CDK8 and confirm CDK8's function in recruiting repressive components, such as G9a, to the RIP140 complex on this ..
  3. Ahuja H, Zhu Y, Zakeri Z. Association of cyclin-dependent kinase 5 and its activator p35 with apoptotic cell death. Dev Genet. 1997;21:258-67 pubmed
    ..Our results suggest a role for Cdk5 and p35 proteins in cell death. This protein complex may function in the rearrangement of the cytoskeleton during apoptosis. ..
  4. Li N, Fassl A, Chick J, Inuzuka H, Li X, Mansour M, et al. Cyclin C is a haploinsufficient tumour suppressor. Nat Cell Biol. 2014;16:1080-91 pubmed publisher
    ..Cyclin C activates an 'orphan' CDK19 kinase, as well as CDK8 and CDK3...
  5. Porter D, Farmaki E, Altilia S, Schools G, West D, Chen M, et al. Cyclin-dependent kinase 8 mediates chemotherapy-induced tumor-promoting paracrine activities. Proc Natl Acad Sci U S A. 2012;109:13799-804 pubmed publisher
    ..These compounds were identified as selective inhibitors of a transcription-regulating kinase CDK8 and its isoform CDK19. Remarkably, p21 was found to bind to CDK8 and stimulate its kinase activity...
  6. Putz E, Gotthardt D, Hoermann G, Csiszar A, Wirth S, Berger A, et al. CDK8-mediated STAT1-S727 phosphorylation restrains NK cell cytotoxicity and tumor surveillance. Cell Rep. 2013;4:437-44 pubmed publisher
    ..Constitutive phosphorylation of S727 depends on cyclin-dependent kinase 8 (CDK8)...
  7. Pavri R, Lewis B, Kim T, Dilworth F, Erdjument Bromage H, Tempst P, et al. PARP-1 determines specificity in a retinoid signaling pathway via direct modulation of mediator. Mol Cell. 2005;18:83-96 pubmed
    ..Importantly, Mediator was inactive (Cdk8+) under basal conditions but was activated (Cdk8-) upon induction...
  8. Malik S, Guermah M, Yuan C, Wu W, Yamamura S, Roeder R. Structural and functional organization of TRAP220, the TRAP/mediator subunit that is targeted by nuclear receptors. Mol Cell Biol. 2004;24:8244-54 pubmed
    ..The implications of these observations are discussed in terms of our present understanding of coactivator function. ..