CDK8

Summary

Gene Symbol: CDK8
Description: cyclin dependent kinase 8
Alias: K35, cyclin-dependent kinase 8, CDK8 protein kinase, cell division protein kinase 8, mediator complex subunit CDK8, mediator of RNA polymerase II transcription subunit CDK8, protein kinase K35
Species: human
Products:     CDK8

Top Publications

  1. Akoulitchev S, Chuikov S, Reinberg D. TFIIH is negatively regulated by cdk8-containing mediator complexes. Nature. 2000;407:102-6 pubmed
    The mammalian cyclin-dependent kinase 8 (cdk8) gene has been linked with a subset of acute lymphoblastic leukaemias, and its corresponding protein has been functionally implicated in regulation of transcription...
  2. Ramanathan Y, Rajpara S, Reza S, Lees E, Shuman S, Mathews M, et al. Three RNA polymerase II carboxyl-terminal domain kinases display distinct substrate preferences. J Biol Chem. 2001;276:10913-20 pubmed
    CDK7, CDK8, and CDK9 are cyclin-dependent kinases (CDKs) that phosphorylate the C-terminal domain (CTD) of RNA polymerase II. They have distinct functions in transcription...
  3. Pinhero R, Liaw P, Bertens K, Yankulov K. Three cyclin-dependent kinases preferentially phosphorylate different parts of the C-terminal domain of the large subunit of RNA polymerase II. Eur J Biochem. 2004;271:1004-14 pubmed
    ..regulated by the phosphorylation of the CTD by three cyclin-dependent protein kinases (CDKs), namely CDK7, CDK8 and CDK9...
  4. Knuesel M, Meyer K, Donner A, Espinosa J, Taatjes D. The human CDK8 subcomplex is a histone kinase that requires Med12 for activity and can function independently of mediator. Mol Cell Biol. 2009;29:650-61 pubmed publisher
    The four proteins CDK8, cyclin C, Med12, and Med13 can associate with Mediator and are presumed to form a stable "CDK8 subcomplex" in cells...
  5. 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...
  6. Tsai K, Sato S, Tomomori Sato C, Conaway R, Conaway J, Asturias F. A conserved Mediator-CDK8 kinase module association regulates Mediator-RNA polymerase II interaction. Nat Struct Mol Biol. 2013;20:611-9 pubmed publisher
    The CDK8 kinase module (CKM) is a conserved, dissociable Mediator subcomplex whose component subunits were genetically linked to the RNA polymerase II (RNAPII) C-terminal domain (CTD) and individually recognized as transcriptional ..
  7. Rickert P, Corden J, Lees E. Cyclin C/CDK8 and cyclin H/CDK7/p36 are biochemically distinct CTD kinases. Oncogene. 1999;18:1093-102 pubmed
    ..We have found that two of these kinases, cyclin C/CDK8 and cyclin H/CDK7/p36, can specifically phosphorylate distinct residues in recombinant CTD substrates...
  8. Taatjes D, Naar A, Andel F, Nogales E, Tjian R. Structure, function, and activator-induced conformations of the CRSP coactivator. Science. 2002;295:1058-62 pubmed
    ..These results suggest that CRSP may potentiate transcription via specific activator-induced conformational changes. ..
  9. Mo X, Kowenz Leutz E, Xu H, Leutz A. Ras induces mediator complex exchange on C/EBP beta. Mol Cell. 2004;13:241-50 pubmed
    ..The CRSP130/Sur2 subunit is common to two distinct types of Mediator complexes, characterized by CRSP70 and CDK8 proteins as transcriptionally active and inactive Mediator, respectively...

More Information

Publications117 found, 100 shown here

  1. Fryer C, White J, Jones K. Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover. Mol Cell. 2004;16:509-20 pubmed
    ..Here we show that CycC:CDK8 and CycT1:CDK9/P-TEFb are recruited with Notch and associated coactivators (MAM, SKIP) to the HES1 promoter in ..
  2. 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...
  3. Donner A, Szostek S, Hoover J, Espinosa J. CDK8 is a stimulus-specific positive coregulator of p53 target genes. Mol Cell. 2007;27:121-33 pubmed
    ..In contrast, three subunits of the CDK module of Mediator (CDK8, MED12, and cyclin C) are exclusively recruited during conditions of strong p21 transcriptional activation...
  4. Meyer K, Donner A, Knuesel M, York A, Espinosa J, Taatjes D. Cooperative activity of cdk8 and GCN5L within Mediator directs tandem phosphoacetylation of histone H3. EMBO J. 2008;27:1447-57 pubmed publisher
    ..does not associate with the transcriptionally active core Mediator but rather with Mediator that contains the cdk8 subcomplex...
  5. Ding N, Zhou H, Esteve P, Chin H, Kim S, Xu X, et al. Mediator links epigenetic silencing of neuronal gene expression with x-linked mental retardation. Mol Cell. 2008;31:347-59 pubmed publisher
    ..These findings implicate Mediator in epigenetic restriction of neuronal gene expression to the nervous system and suggest a pathologic basis for MED12-associated XLMR involving impaired REST-dependent neuronal gene regulation. ..
  6. Morris E, Ji J, Yang F, Di Stefano L, Herr A, Moon N, et al. E2F1 represses beta-catenin transcription and is antagonized by both pRB and CDK8. Nature. 2008;455:552-6 pubmed publisher
    ..Remarkably, E2F1 activity is also repressed by cyclin-dependent kinase-8 (CDK8), a colorectal oncoprotein...
  7. Firestein R, Bass A, Kim S, Dunn I, Silver S, Guney I, et al. CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity. Nature. 2008;455:547-51 pubmed publisher
    ..One of these genes, CDK8, which encodes a member of the mediator complex, is located at 13q12...
  8. Donner A, Ebmeier C, Taatjes D, Espinosa J. CDK8 is a positive regulator of transcriptional elongation within the serum response network. Nat Struct Mol Biol. 2010;17:194-201 pubmed publisher
    ..Cyclin-dependent kinase 8 (CDK8), the kinase found in some variants of Mediator, has been characterized mostly as a transcriptional repressor...
  9. Schneider E, Bottcher J, Blaesse M, Neumann L, Huber R, Maskos K. The structure of CDK8/CycC implicates specificity in the CDK/cyclin family and reveals interaction with a deep pocket binder. J Mol Biol. 2011;412:251-66 pubmed publisher
    ..b>CDK8 is involved in the regulation of mRNA transcription and was identified as a potent oncogene in colon cancerogenesis...
  10. Gupta E, Pachauri M, Ghosh P, Rajam M. Targeting polyamine biosynthetic pathway through RNAi causes the abrogation of MCF 7 breast cancer cell line. Tumour Biol. 2016;37:1159-71 pubmed publisher
    ..apoptosis-related genes, it was observed that RNAi against PA biosynthetic genes downregulated the expression of CDK8, CCNE2, CCNH, CCNT1, CCNT2, CCNF, PCNA, CCND1, and CDK2, and upregulated the expression of E2F4, BAX, FAS, TP53, ..
  11. Peña Hernández R, Marques M, Hilmi K, Zhao T, Saad A, Alaoui Jamali M, et al. Genome-wide targeting of the epigenetic regulatory protein CTCF to gene promoters by the transcription factor TFII-I. Proc Natl Acad Sci U S A. 2015;112:E677-86 pubmed publisher
    ..CTCF and TFII-I, we find knockdown of TFII-I results in diminished CTCF binding, lack of cyclin-dependent kinase 8 (CDK8) recruitment, and an attenuation of RNA polymerase II phosphorylation at serine 5...
  12. Yang P, Yin K, Zhong D, Liao Q, Li K. Inhibition of osteosarcoma cell progression by MacroH2A via the downregulation of cyclin D and cyclin‑dependent kinase genes. Mol Med Rep. 2015;11:1905-10 pubmed publisher
    ..of cyclin D and cyclin‑dependent kinase (CDK) genes, including cyclin D1, cyclin D2, CDK4, CDK6 and CDK8. Taken together, the present results revealed that MacroH2A is an important modifier of chromatin that ..
  13. Kämpjärvi K, Kim N, Keskitalo S, Clark A, von Nandelstadh P, Turunen M, et al. Somatic MED12 mutations in prostate cancer and uterine leiomyomas promote tumorigenesis through distinct mechanisms. Prostate. 2016;76:22-31 pubmed publisher
    ..the L1224F mutation compromises neither the interaction of MED12 with kinase module subunits Cyclin C and CDK8/19 nor Mediator-associated CDK activity...
  14. Willger S, Liu Z, Olarte R, Adamo M, Stajich J, Myers L, et al. Analysis of the Candida albicans Phosphoproteome. Eukaryot Cell. 2015;14:474-85 pubmed publisher
    ..studies, and further in vitro assays identified a subset of these phosphorylations that were catalyzed by Cdk8 (Ssn3), a kinase within the Mediator complex...
  15. Poss Z, Ebmeier C, Taatjes D. The Mediator complex and transcription regulation. Crit Rev Biochem Mol Biol. 2013;48:575-608 pubmed publisher
    ..We also describe factors that influence Mediator structure and activity, including TFs, non-coding RNAs and the CDK8 module.
  16. Doğan Şığva Z, Balci Okcanoglu T, Biray Avci C, Yilmaz Susluer S, Kayabasi C, Turna B, et al. Investigation of the synergistic effects of paclitaxel and herbal substances and endemic plant extracts on cell cycle and apoptosis signal pathways in prostate cancer cell lines. Gene. 2019;687:261-271 pubmed publisher
    ..Besides, they increased the expression of TNFRSF10A, TNFRSF1A, CHEK1, CDKN1A, CDKN2B, CDK8, CDKN3 and CASP14 and decreased BAD, CDK5RAP1, CDC20, cyclin H, CDK5RAP1, CDC20...
  17. Songock W, Scott M, Bodily J. Regulation of the human papillomavirus type 16 late promoter by transcriptional elongation. Virology. 2017;507:179-191 pubmed publisher
    ..Three factors that promote transcript elongation, cyclin dependent kinase 9 (CDK9), CDK8 (a subunit of the Mediator complex), and bromodomain containing protein 4 (Brd4) are recruited to viral genomes ..
  18. Kong X, Duan L, Qian X, Xu D, Liu H, Zhu Y, et al. Tumor-suppressive microRNA-497 targets IKKβ to regulate NF-κB signaling pathway in human prostate cancer cells. Am J Cancer Res. 2015;5:1795-804 pubmed
    ..Finally, similar results was found after treatment with a novel IKK-β inhibitor (IMD-0354) in PC3-AR cells. CDK8, MMP-9, and PSA were involved in all these process...
  19. Kämpjärvi K, Park M, Mehine M, Kim N, Clark A, Bützow R, et al. Mutations in Exon 1 highlight the role of MED12 in uterine leiomyomas. Hum Mutat. 2014;35:1136-41 pubmed publisher
    ..activity assays showed that both exon 1 and exon 2 mutations disrupt the interaction between MED12 and Cyclin C and CDK8/19 and abolish the mediator-associated CDK kinase activity...
  20. Cao J, Xu G, Lan J, Huang Q, Tang Z, Tian L. High expression of piwi-like RNA-mediated gene silencing 1 is associated with poor prognosis via regulating transforming growth factor-β receptors and cyclin-dependent kinases in breast cancer. Mol Med Rep. 2016;13:2829-35 pubmed publisher
    ..growth factor‑β receptor (TβR)I, TβRII, cyclin‑dependent kinase (CDK)4, CDK6 and CDK8 were observed to be regulated by HIWI, which indicated a novel mechanism of HIWI in the regulation of breast cancer ..
  21. Jean Jacques H, Poh S, Kuras L. Mediator, known as a coactivator, can act in transcription initiation in an activator-independent manner in vivo. Biochim Biophys Acta Gene Regul Mech. 2018;1861:687-696 pubmed publisher
    ..absence of activator: (i) Mediator can associate with a promoter as a form devoid of the Cyclin-dependent kinase 8 (CDK8) module, and this association remains regulated by Kin28; (ii) Mediator can stimulate the assembly of the entire ..
  22. Snijders Blok L, Hiatt S, Bowling K, Prokop J, Engel K, Cochran J, et al. De novo mutations in MED13, a component of the Mediator complex, are associated with a novel neurodevelopmental disorder. Hum Genet. 2018;137:375-388 pubmed publisher
    ..Thr326 and p.Pro327. MED13 is a component of the CDK8-kinase module that can reversibly bind Mediator, a multi-protein complex that is required for Polymerase II ..
  23. Friedrichs P, Schlotterer A, Sticht C, Kolibabka M, Wohlfart P, Dietrich A, et al. Hyperglycaemic memory affects the neurovascular unit of the retina in a diabetic mouse model. Diabetologia. 2017;60:1354-1358 pubmed publisher
    ..Myl12b, Dynll1, Stag3 and Sntg2, and in the nuclear compartment were Ddx51, Utp23, Mnda, Kmt2e, Nr6a1, Parp2, Cdk8, Srsf1 and Zfp326...
  24. Gärtner A, Wagner K, Hölper S, Kunz K, Rodriguez M, Muller S. Acetylation of SUMO2 at lysine 11 favors the formation of non-canonical SUMO chains. EMBO Rep. 2018;19: pubmed publisher
    ..Importantly, mimicking K11 acetylation alters chain architecture by favoring K5- and K35-linked chains, while inhibiting K7 and K21 linkages...
  25. Kakkar S, Kumar S, Lim S, Ramasamy K, Mani V, Shah S, et al. Design, synthesis and biological evaluation of 3-(2-aminooxazol-5-yl)-2H-chromen-2-one derivatives. Chem Cent J. 2018;12:130 pubmed publisher
    ..the molecular docking study has been carried to find out the interaction between active oxazole compounds with CDK8 (HCT116) and ER-α (MCF7) proteins indicated that compound 14 and 6 showed good dock score with better potency ..
  26. Feng L, Cook B, Tsai S, Zhou T, LaFlamme B, Evans T, et al. Discovery of a Small-Molecule BMP Sensitizer for Human Embryonic Stem Cell Differentiation. Cell Rep. 2016;15:2063-75 pubmed publisher
    ..Additional mechanistic studies indicate that CHK1 inhibition depletes p21 levels, thereby activating CDK8/9, which then phosphorylates the SMAD2/3 linker region, leading to decreased levels of SMAD2/3 protein and enhanced ..
  27. Kämpjärvi K, Järvinen T, Heikkinen T, Ruppert A, Senter L, Hoag K, et al. Somatic MED12 mutations are associated with poor prognosis markers in chronic lymphocytic leukemia. Oncotarget. 2015;6:1884-8 pubmed
    ..Functional analyses have shown that these mutations lead to dissociation of Cyclin C-CDK8/19 from the core Mediator and to the loss of Mediator-associated CDK kinase activity...
  28. Perez Perri J, Dengler V, Audetat K, Pandey A, Bonner E, Urh M, et al. The TIP60 Complex Is a Conserved Coactivator of HIF1A. Cell Rep. 2016;16:37-47 pubmed publisher
    ..cells, global analysis of HIF1A-dependent gene activity reveals that most HIF1A targets require either TIP60, the CDK8-Mediator complex, or both as coactivators for full expression in hypoxia...
  29. Giangregorio N, Console L, Tonazzi A, Palmieri F, Indiveri C. Identification of amino acid residues underlying the antiport mechanism of the mitochondrial carnitine/acylcarnitine carrier by site-directed mutagenesis and chemical labeling. Biochemistry. 2014;53:6924-33 pubmed publisher
    ..This substrate-induced conformational change was abolished in the protein lacking K35, pointing to the role of this residue as a sensor in the mechanism of the antiport reaction.
  30. Khan I, Seebald L, Robertson N, Yigit M, Royzen M. Controlled in-cell activation of RNA therapeutics using bond-cleaving bio-orthogonal chemistry. Chem Sci. 2017;8:5705-5712 pubmed publisher
    ..our in-cell activation approach using two siRNAs against green fluorescent protein (GFP) and cyclin dependent kinase 8 (CDK8) in GFP expressing MDA-MB-231 cell line...
  31. Morse D, Daoust P, Benribague S. A Transcriptome-based Perspective of Cell Cycle Regulation in Dinoflagellates. Protist. 2016;167:610-621 pubmed publisher
    ..the dinoflagellates contain at least three cyclin-dependent kinase (CDK) homologs (belonging to the CDK1, CDK5 and CDK8 families), and that the dinoflagellate cyclins belong exclusively to the A/B type...
  32. Kong X, Qian X, Duan L, Liu H, Zhu Y, Qi J. microRNA-372 Suppresses Migration and Invasion by Targeting p65 in Human Prostate Cancer Cells. DNA Cell Biol. 2016;35:828-835 pubmed
    ..b>CDK8, MMP-9, and prostate-specific antigen were involved in both these processes...
  33. Ross D, Gulliver D. Reconstruction of a Nearly Complete Pseudomonas Draft Genome Sequence from a Coalbed Methane-Produced Water Metagenome. Genome Announc. 2016;4: pubmed publisher
    The draft genome sequence of Pseudomonas stutzeri strain K35 was separated from a metagenome derived from a produced water microbial community of a coalbed methane well...
  34. Buendía Monreal M, Gillmor C. Convergent repression of miR156 by sugar and the CDK8 module of Arabidopsis Mediator. Dev Biol. 2017;423:19-23 pubmed publisher
    ..Both leaf derived sugars, as well as the Mediator Cyclin Dependent Kinase 8 (CDK8) module genes CENTER CITY (CCT)/MED12 and GRAND CENTRAL (GCT)/MED13, act upstream of miR156 to ..
  35. Pinhero R, Liaw P, Yankulov K. A uniform procedure for the purification of CDK7/CycH/MAT1, CDK8/CycC and CDK9/CycT1. Biol Proced Online. 2004;6:163-172 pubmed
    ..established a uniform procedure for the expression and purification of the cyclin-dependent kinases CDK7/CycH/MAT1, CDK8/CycC and CDK9/CycT1...
  36. 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 ..
  37. Cai W, Shen F, Feng Z, Chen J, Liu Q, Li E, et al. Downregulation of CDK-8 inhibits colon cancer hepatic metastasis by regulating Wnt/β-catenin pathway. Biomed Pharmacother. 2015;74:153-7 pubmed publisher
    ..To investigate the role of cyclin-dependent kinase 8 (CDK8) in the progression of colon cancer hepatic metastasis...
  38. Kumar S, Lim S, Ramasamy K, Vasudevan M, Shah S, Selvaraj M, et al. Synthesis, molecular docking and biological evaluation of bis-pyrimidine Schiff base derivatives. Chem Cent J. 2017;11:89 pubmed publisher
    ..information regarding the binding mode of active bis-pyrimidine Schiff bases with the cyclin-dependent kinase 8 (CDK8) receptor. The antimicrobial screening results indicated that compounds, q1 (MICbs = 0...
  39. Han C, Zheng W, Ge M, Wang K, Xiang Y, Wang P. Downregulation of cyclin-dependent kinase 8 by microRNA-148a suppresses proliferation and invasiveness of papillary thyroid carcinomas. Am J Cancer Res. 2017;7:2081-2090 pubmed
    ..We have identified the cyclin-dependent kinase 8 (CDK8) gene as a direct target of miR-148a using the online software packages TargetScan and miRanda...
  40. Long N, Zeng L, Qiao S, Li L, Zhong G. Aspergillus fumigatus Afssn3-Afssn8 Pair Reverse Regulates Azole Resistance by Conferring Extracellular Polysaccharide, Sphingolipid Pathway Intermediates, and Efflux Pumps to Biofilm. Antimicrob Agents Chemother. 2018;62: pubmed publisher
    ..reverse genetic strategy, we identified that nucleus-localized AfSsn3 and its partner AfSsn8, which constitute a Cdk8-cyclin pair, are required for azole resistance in Aspergillus fumigatus Deletion of Afssn3 led to ..
  41. Xie X, Hsu F, Gao X, Xu W, Ni J, Xing Y, et al. CDK8-Cyclin C Mediates Nutritional Regulation of Developmental Transitions through the Ecdysone Receptor in Drosophila. PLoS Biol. 2015;13:e1002207 pubmed publisher
    ..Here, we show that EcR-dependent transcription, and thus, developmental timing in Drosophila, is regulated by CDK8 and its regulatory partner Cyclin C (CycC), and the level of CDK8 is affected by nutrient availability...
  42. Crowley T, Kaine E, Yoshida M, Nandi A, Wolgemuth D. Reproductive cycle regulation of nuclear import, euchromatic localization, and association with components of Pol II mediator of a mammalian double-bromodomain protein. Mol Endocrinol. 2002;16:1727-37 pubmed
    ..Localization of Fsrg1 on euchromatin, the transcribed portion of the chromosomes, is consistent with its hypothesized function as a transcription regulator. ..
  43. Hassa P, Haenni S, Buerki C, Meier N, Lane W, Owen H, et al. Acetylation of poly(ADP-ribose) polymerase-1 by p300/CREB-binding protein regulates coactivation of NF-kappaB-dependent transcription. J Biol Chem. 2005;280:40450-64 pubmed
    ..Thus, acetylation of PARP-1 by p300/CREB-binding protein plays an important regulatory role in NF-kappaB-dependent gene activation by enhancing its functional interaction with p300 and the Mediator complex. ..
  44. Tsutsui T, Ohkuma Y. [Mechanisms of transcriptional regulation upon protein phosphorylation by mediator complexes]. Seikagaku. 2010;82:191-9 pubmed
  45. Wang J, Ni J, Yi S, Song D, Ding M. Protein inhibitor of activated STAT xα depresses cyclin D and cyclin D kinase, and contributes to the inhibition of osteosarcoma cell progression. Mol Med Rep. 2016;13:1645-52 pubmed publisher
    ..Accordingly, cyclin D kinase (CDK) genes, including CDK4, CDK6 and CDK8, increased markedly following treatment with PIAsxα siRNAs...
  46. Mallinger A, Schiemann K, Rink C, Stieber F, Calderini M, Crumpler S, et al. Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19. J Med Chem. 2016;59:1078-101 pubmed publisher
    The Mediator complex-associated cyclin-dependent kinase CDK8 has been implicated in human disease, particularly in colorectal cancer where it has been reported as a putative oncogene...
  47. McDermott M, Chumanevich A, Lim C, Liang J, Chen M, Altilia S, et al. Inhibition of CDK8 mediator kinase suppresses estrogen dependent transcription and the growth of estrogen receptor positive breast cancer. Oncotarget. 2017;8:12558-12575 pubmed publisher
    ..Cyclin-dependent kinase 8 (CDK8) is a Mediator complex-associated transcriptional regulator with oncogenic activities...
  48. Kuuluvainen E, Domènech Moreno E, Niemelä E, Makela T. Depletion of Mediator Kinase Module Subunits Represses Superenhancer-Associated Genes in Colon Cancer Cells. Mol Cell Biol. 2018;38: pubmed publisher
    ..of superenhancer gene expression, this was not seen with depletion of the kinases cyclin-dependent kinase 9 (CDK8) and CDK19...
  49. Mittler G, Stühler T, Santolin L, Uhlmann T, Kremmer E, Lottspeich F, et al. A novel docking site on Mediator is critical for activation by VP16 in mammalian cells. EMBO J. 2003;22:6494-504 pubmed
    ..Despite many known targets of VP16, ARC92/ACID1 appears to impose a critical control on transcription activation by VP16 in mammalian cells. ..
  50. Xu W, Ji J. Dysregulation of CDK8 and Cyclin C in tumorigenesis. J Genet Genomics. 2011;38:439-52 pubmed publisher
    ..Here we focus our discussion on two subunits of the Mediator complex, cyclin-dependent kinase 8 (CDK8) and its regulatory partner Cyclin C (CycC), because they are either mutated or amplified in a variety of human ..
  51. Rovnak J, Brewster C, Quackenbush S. Retroviral cyclin enhances cyclin-dependent kinase-8 activity. J Virol. 2012;86:5742-51 pubmed publisher
    Alterations in the functional levels of cyclin-dependent kinase-8 (CDK8) or its partner, cyclin C, have been clearly associated with cancers, including colon cancer, melanoma, and osteosarcoma...
  52. Brägelmann J, Klümper N, Offermann A, von Mässenhausen A, Böhm D, Deng M, et al. Pan-Cancer Analysis of the Mediator Complex Transcriptome Identifies CDK19 and CDK8 as Therapeutic Targets in Advanced Prostate Cancer. Clin Cancer Res. 2017;23:1829-1840 pubmed publisher
    ..The role of CDK19 and CDK8 was evaluated by siRNA-mediated gene knockdown and inhibitor treatment in prostate cancer cell lines with ..
  53. Paparidis N, Durvale M, Canduri F. The emerging picture of CDK9/P-TEFb: more than 20 years of advances since PITALRE. Mol Biosyst. 2017;13:246-276 pubmed publisher
    ..CDK9/P-TEFb phosphorylates the C-terminal domain of RNAP II in the same positions targeted by CDK7 (TFIIH) and CDK8 (Mediator), the former does not participate in the transcription initiation, but rather plays a unique role by ..
  54. Wang T, Yang Z, Zhang Y, Yan W, Wang F, He L, et al. Discovery of novel CDK8 inhibitors using multiple crystal structures in docking-based virtual screening. Eur J Med Chem. 2017;129:275-286 pubmed publisher
    The cyclin dependent kinase CDK8, along with Med12 and Med13, form the kinase module of the Mediator complex. CDK8 expression associates with the activation of ?-catenin in colon and gastric cancers...
  55. Han X, Jiang M, Zhou C, Zhou Z, Xu Z, Wang L, et al. Discovery of potent and selective CDK8 inhibitors through FBDD approach. Bioorg Med Chem Lett. 2017;27:4488-4492 pubmed publisher
    A fragment library screen was carried out to identify starting points for novel CDK8 inhibitors...
  56. Tang H, Hu Y, Chen C, Xia B, ZIRIN J, Yuan M, et al. The TORC1-Regulated CPA Complex Rewires an RNA Processing Network to Drive Autophagy and Metabolic Reprogramming. Cell Metab. 2018;27:1040-1054.e8 pubmed publisher
    ..We show that TORC1 signaling inhibits CDK8 and DOA kinases, which directly phosphorylate CPSF6, a component of the CPA complex...
  57. Wang G, Cantin G, Stevens J, Berk A. Characterization of mediator complexes from HeLa cell nuclear extract. Mol Cell Biol. 2001;21:4604-13 pubmed
    ..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 ..
  58. Aragón E, Goerner N, Zaromytidou A, Xi Q, Escobedo A, Massagué J, et al. A Smad action turnover switch operated by WW domain readers of a phosphoserine code. Genes Dev. 2011;25:1275-88 pubmed publisher
    When directed to the nucleus by TGF-? or BMP signals, Smad proteins undergo cyclin-dependent kinase 8/9 (CDK8/9) and glycogen synthase kinase-3 (GSK3) phosphorylations that mediate the binding of YAP and Pin1 for transcriptional action, ..
  59. Fisher R. Taking Aim at Glycolysis with CDK8 Inhibitors. Trends Endocrinol Metab. 2018;29:281-282 pubmed publisher
    ..Now, through chemical genetics, CDK8, a kinase associated with the Mediator transcriptional coactivator complex, has emerged as an upstream inducer of ..
  60. Fukasawa R, Tsutsui T, Hirose Y, Tanaka A, Ohkuma Y. Mediator CDK subunits are platforms for interactions with various chromatin regulatory complexes. J Biochem. 2012;152:241-9 pubmed publisher
    ..Many studies, including our own, have revealed that CDK8, a kinase subunit of the CDK/Cyclin module, is one of the key subunits involved in these roles...
  61. 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...
  62. Yamamoto S, Hagihara T, Horiuchi Y, Okui A, Wani S, Yoshida T, et al. Mediator cyclin-dependent kinases upregulate transcription of inflammatory genes in cooperation with NF-?B and C/EBP? on stimulation of Toll-like receptor 9. Genes Cells. 2017;22:265-276 pubmed publisher
    ..Among them, CDK8 and/or CDK19 (CDK8/19), and their counterpart cyclin C, form the CDK/cyclin module together with Mediator subunits ..
  63. Shashkov A, Liu B, Kenyon J, Popova A, Shneider M, Senchenkova S, et al. Structures of the K35 and K15 capsular polysaccharides of Acinetobacter baumannii LUH5535 and LUH5554 containing amino and diamino uronic acids. Carbohydr Res. 2017;448:28-34 pubmed publisher
    Capsular polysaccharides were isolated from A. baumannii LUH5535 (K35 CPS) and LUH5554 (K15 CPS) and studied by 1D and 2D 1H and 13C NMR spectroscopy...
  64. Stieg D, Willis S, Ganesan V, Ong K, Scuorzo J, Song M, et al. A complex molecular switch directs stress-induced cyclin C nuclear release through SCFGrr1-mediated degradation of Med13. Mol Biol Cell. 2018;29:363-375 pubmed publisher
    ..The conserved cyclin C and its kinase partner Cdk8 play a key role in this decision...
  65. Zhang X, Zhang X, Wang T, Wang L, Tan Z, Wei W, et al. MicroRNA-26a is a key regulon that inhibits progression and metastasis of c-Myc/EZH2 double high advanced hepatocellular carcinoma. Cancer Lett. 2018;426:98-108 pubmed publisher
    ..c-Myc, a classical Wnt pathway target gene, by targeting the Wnt pathway coactivator, cyclin-dependent kinase 8 (CDK8); miR-26a also directly targets and inhibits EZH2...
  66. Tassan J, Jaquenoud M, Leopold P, Schultz S, Nigg E. Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C. Proc Natl Acad Sci U S A. 1995;92:8871-5 pubmed
    ..Here we report the identification of a human protein kinase, K35 [cyclin-dependent kinase 8 (CDK8)], that is likely to be a physiological partner of cyclin C...
  67. Pan G, Aso T, Greenblatt J. Interaction of elongation factors TFIIS and elongin A with a human RNA polymerase II holoenzyme capable of promoter-specific initiation and responsive to transcriptional activators. J Biol Chem. 1997;272:24563-71 pubmed
    ..It also contained the cyclin-dependent kinase CDK8, a human homologue of the Saccharomyces cerevisiae holoenzyme subunit SRB10, and many other polypeptides...
  68. Gu W, Malik S, Ito M, Yuan C, Fondell J, Zhang X, et al. A novel human SRB/MED-containing cofactor complex, SMCC, involved in transcription regulation. Mol Cell. 1999;3:97-108 pubmed
    ..These findings demonstrate both positive and negative functional capabilities for the human complex, emphasize novel (CTD-independent) regulatory mechanisms, and link the complex to other human coactivator complexes. ..
  69. Di Pietro C, Rapisarda A, Bonaiuto C, Lizzio M, Engel H, Amico V, et al. Genomics of the human genes encoding four TAFII subunits of TFIID, the three subunits of TFIIA, as well as CDK8 and SURB7. Somat Cell Mol Genet. 1999;25:185-9 pubmed
    ..TAFII68, TAFII18), the three subunits of TFIIA (TFIIA35 and TFIIA19, both encoded by the same gene, and TFIIA12), CDK8, and SURB7...
  70. Yang F, Vought B, Satterlee J, Walker A, Jim Sun Z, Watts J, et al. An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis. Nature. 2006;442:700-4 pubmed
    ..Taken together, our findings demonstrate that ARC105 is a key effector of SREBP-dependent gene regulation and control of lipid homeostasis in metazoans. ..
  71. Furumoto T, Tanaka A, Ito M, Malik S, Hirose Y, Hanaoka F, et al. A kinase subunit of the human mediator complex, CDK8, positively regulates transcriptional activation. Genes Cells. 2007;12:119-32 pubmed
    ..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 ..
  72. 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 ..
  73. 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...
  74. Tsutsui T, Fukasawa R, Shinmyouzu K, Nakagawa R, Tobe K, Tanaka A, et al. Mediator complex recruits epigenetic regulators via its two cyclin-dependent kinase subunits to repress transcription of immune response genes. J Biol Chem. 2013;288:20955-65 pubmed publisher
    ..First, we purified CDK8- and CDK19-containing complexes from HeLa nuclear extracts and subjected these purified complexes to mass ..
  75. Aristizabal M, Negri G, Benschop J, Holstege F, Krogan N, Kobor M. High-throughput genetic and gene expression analysis of the RNAPII-CTD reveals unexpected connections to SRB10/CDK8. PLoS Genet. 2013;9:e1003758 pubmed publisher
    ..The mediator subunit Cdk8 was enriched at promoters of these genes, and its removal not only restored normal mRNA and RNAPII occupancy levels,..
  76. Li M, Tian L, Ren H, Chen X, Wang Y, Ge J, et al. MicroRNA-101 is a potential prognostic indicator of laryngeal squamous cell carcinoma and modulates CDK8. J Transl Med. 2015;13:271 pubmed publisher
    ..Moreover, we identified Cyclin-dependent kinase 8 (CDK8) as the target of miR-101 by a luciferase assay...
  77. Pelish H, Liau B, Nitulescu I, Tangpeerachaikul A, Poss Z, Da Silva D, et al. Mediator kinase inhibition further activates super-enhancer-associated genes in AML. Nature. 2015;526:273-276 pubmed publisher
    ..Here we show that the Mediator-associated kinases cyclin-dependent kinase 8 (CDK8) and CDK19 restrain increased activation of key SE-associated genes in acute myeloid leukaemia (AML) cells...
  78. Li M, Zhao X, Liu Y, An J, Xiao H, Wang C. Aberrant expression of CDK8 regulates the malignant phenotype and associated with poor prognosis in human laryngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol. 2017;274:2205-2213 pubmed publisher
    b>CDK8, a member of the transcriptional subtype of the cyclin-dependent kinases (CDKs) family, shows remarkable cancer tissue specific expression profile and rather more selective contribution to the regulation of gene expression levels ..
  79. Ono K, Banno H, Okaniwa M, Hirayama T, Iwamura N, Hikichi Y, et al. Design and synthesis of selective CDK8/19 dual inhibitors: Discovery of 4,5-dihydrothieno[3',4':3,4]benzo[1,2-d]isothiazole derivatives. Bioorg Med Chem. 2017;25:2336-2350 pubmed publisher
    To develop a novel series of CDK8/19 dual inhibitors, we employed structure-based drug design using docking models based on a library compound, 4,5-dihydroimidazolo[3',4':3,4]benzo[1,2-d]isothiazole 16 bound to CDK8...
  80. Bruno S, Tapparo M, Collino F, Chiabotto G, Deregibus M, Soares Lindoso R, et al. Renal Regenerative Potential of Different Extracellular Vesicle Populations Derived from Bone Marrow Mesenchymal Stromal Cells. Tissue Eng Part A. 2017;23:1262-1273 pubmed publisher
    ..The 100K population, for instance, was enriched in specific mRNAs (CCNB1, CDK8, CDC6) reported to influence cell cycle entry and progression; miRNAs involved in regulating proliferative/..
  81. Banyai G, Szilagyi Z, Baraznenok V, Khorosjutina O, Gustafsson C. Cyclin C influences the timing of mitosis in fission yeast. Mol Biol Cell. 2017;28:1738-1744 pubmed publisher
    ..Mediator contains the Cdk8 regulatory subcomplex, which directs periodic transcription and influences cell cycle progression in fission yeast...
  82. Giagulli C, D Ursi P, He W, Zorzan S, Caccuri F, Varney K, et al. A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Sci Rep. 2017;7:6555 pubmed publisher
    ..CASP-9, CASP-7, DFF-45, NPM, YWHAZ, Src, PAX2, MAPK8), cell cycle promotion and cancer progression (CDK1, CDK2, CDK8, CHEK1, CHEK2, GSK-3 beta, NPM, PAK1, PP2C-alpha)...
  83. Wu B, SÅ‚abicki M, Sellner L, Dietrich S, Liu X, Jethwa A, et al. MED12 mutations and NOTCH signalling in chronic lymphocytic leukaemia. Br J Haematol. 2017;179:421-429 pubmed publisher
    ..MED12 mutations have been previously linked to aberrant Cyclin C-CDK8 kinase activity, but the exact oncogenic function in CLL is unknown...
  84. Schultz S, Nigg E. Identification of 21 novel human protein kinases, including 3 members of a family related to the cell cycle regulator nimA of Aspergillus nidulans. Cell Growth Differ. 1993;4:821-30 pubmed
  85. Scully R, Anderson S, Chao D, Wei W, Ye L, Young R, et al. BRCA1 is a component of the RNA polymerase II holoenzyme. Proc Natl Acad Sci U S A. 1997;94:5605-10 pubmed
    ..These data are consistent with recent data identifying transcription activation domains in the BRCA1 protein and link the BRCA1 tumor suppressor protein with the transcription process as a holoenzyme-bound protein. ..
  86. Suñé C, Hayashi T, Liu Y, Lane W, Young R, Garcia Blanco M. CA150, a nuclear protein associated with the RNA polymerase II holoenzyme, is involved in Tat-activated human immunodeficiency virus type 1 transcription. Mol Cell Biol. 1997;17:6029-39 pubmed
    ..Furthermore, we found that functional Tat associates with the holoenzyme whereas activation-deficient Tat mutants do not. Thus, we propose that Tat action is transduced via an RNA polymerase II holoenzyme that contains CA150. ..
  87. Ito M, Yuan C, Malik S, Gu W, Fondell J, Yamamura S, et al. Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators. Mol Cell. 1999;3:361-70 pubmed
    ..Identification of the TRAP230 subunit as a previously predicted gene product also suggests a coactivator-related transcription defect in certain disease states. ..
  88. Boyer T, Martin M, Lees E, Ricciardi R, Berk A. Mammalian Srb/Mediator complex is targeted by adenovirus E1A protein. Nature. 1999;399:276-9 pubmed
    ..Interaction with human Sur-2 is also required for transcription to be activated by the activation domain of a transcription factor of the ETS-family in response to activated mitogen-activated protein (MAP) kinase. ..
  89. Vogel L, Baratte B, Detivaud L, Azzi L, Leopold P, Meijer L. Molecular cloning and characterisation of p15(CDK-BP), a novel CDK-binding protein. Biochim Biophys Acta. 2002;1589:219-31 pubmed
    ..In addition p15B interacts tightly with CDK4, CDK6, CDK8 and the yeast CDC28-related kinase Pho85, but not with CDK1, CDK2 or CDK7...
  90. Seo J, Han S, Lim S. Role of CDK8 and beta-catenin in colorectal adenocarcinoma. Oncol Rep. 2010;24:285-91 pubmed
    ..However, relatively little is known about the regulatory mechanism of beta-catenin in colon cancers. CDK8 is a cyclin-dependent kinase (CDK) member of the mediator complex that couples transcriptional regulators to the ..
  91. Brewster C, Birkenheuer C, Vogt M, Quackenbush S, Rovnak J. The retroviral cyclin of walleye dermal sarcoma virus binds cyclin-dependent kinases 3 and 8. Virology. 2011;409:299-307 pubmed publisher
    ..Co-immune precipitation (co-IP) identified an association of rv-cyclin with cyclin-dependent kinase 8 (cdk8)...
  92. Zhao J, Ramos R, Demma M. CDK8 regulates E2F1 transcriptional activity through S375 phosphorylation. Oncogene. 2013;32:3520-30 pubmed publisher
    ..A key mediator of this activation is the recently described oncogene CDK8, which is amplified in a large number of colorectal tumors...