Cyclin-dependent kinase 8

Cyclin-dependent kinase 8
Identifiers
Symbols	CDK8; K35; MGC126074; MGC126075
External IDs	OMIM: 603184 MGI: 1196224 HomoloGene: 55565 GeneCards: CDK8 Gene
Gene Ontology Molecular function • nucleotide binding • protein kinase activity • cyclin-dependent protein kinase activity • protein binding • ATP binding • RNA polymerase II carboxy-terminal domain kinase activity Cellular component • nucleus • nucleoplasm • mediator complex Biological process • regulation of transcription, DNA-dependent • protein phosphorylation • gene expression Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1024	264064
Ensembl	ENSG00000132964	ENSMUSG00000029635
UniProt	P49336	n/a
RefSeq (mRNA)	NM_001260	NM_153599.3
RefSeq (protein)	NP_001251	NP_705827.2
Location (UCSC)	Chr 13: 26.83 – 26.98 Mb	Chr 5: 147.04 – 147.11 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. CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28, and Schizosaccharomyces pombe cdc2, and are known to be important regulators of cell cycle progression. This kinase and its regulatory subunit cyclin C are components of the RNA polymerase II holoenzyme complex, which phosphorylates the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II. This kinase has also been shown to regulate transcription by targeting the CDK7/cyclin H subunits of the general transcription initiation factor IIH (TFIIH), thus providing a link between the 'Mediator-like' protein complexes and the basal transcription machinery.^[2]

Interactions

Cyclin-dependent kinase 8 has been shown to interact with MED16,^[3][4] MED26,^[5] MED17,^[3][4] MED14,^[6][3] CREB binding protein,^[7] MED1,^[3][4] MED6,^[8][6][3][4] MED24,^[3][4] CCNC,^{[9][7][6][4][1]} POLR2A,^[7] MED21,^{[7][10][3][4]} SMARCB1,^[7] MED12^[3][4] and CRSP3.^[6][4]

References

1. ^ ^{a b} Tassan JP, Jaquenoud M, Leopold P, Schultz SJ, Nigg EA (Oct 1995). "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proc Natl Acad Sci U S A 92 (19): 8871–5. doi:10.1073/pnas.92.19.8871. PMC 41069. PMID 7568034. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=41069. 
2. ^ ^{a b} "Entrez Gene: CDK8 cyclin-dependent kinase 8". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1024. 
3. ^ ^{a b c d e f g h} Ito, M; Yuan C X, Malik S, Gu W, Fondell J D, Yamamura S, Fu Z Y, Zhang X, Qin J, Roeder R G (Mar. 1999). "Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators". Mol. Cell (UNITED STATES) 3 (3): 361–70. doi:10.1016/S1097-2765(00)80463-3. ISSN 1097-2765. PMID 10198638. 
4. ^ ^{a b c d e f g h i} Kang, Yun Kyoung; Guermah Mohamed, Yuan Chao-Xing, Roeder Robert G (Mar. 2002). "The TRAP/Mediator coactivator complex interacts directly with estrogen receptors α and β through the TRAP220 subunit and directly enhances estrogen receptor function in vitro". Proc. Natl. Acad. Sci. U.S.A. (United States) 99 (5): 2642–7. doi:10.1073/pnas.261715899. ISSN 0027-8424. PMC 122401. PMID 11867769. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=122401. 
5. ^ Sato, Shigeo; Tomomori-Sato Chieri, Parmely Tari J, Florens Laurence, Zybailov Boris, Swanson Selene K, Banks Charles A S, Jin Jingji, Cai Yong, Washburn Michael P, Conaway Joan Weliky, Conaway Ronald C (Jun. 2004). "A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology". Mol. Cell (United States) 14 (5): 685–91. doi:10.1016/j.molcel.2004.05.006. ISSN 1097-2765. PMID 15175163. 
6. ^ ^{a b c d} Wang, G; Cantin G T, Stevens J L, Berk A J (Jul. 2001). "Characterization of Mediator Complexes from HeLa Cell Nuclear Extract". Mol. Cell. Biol. (United States) 21 (14): 4604–13. doi:10.1128/MCB.21.14.4604-4613.2001. ISSN 0270-7306. PMC 87123. PMID 11416138. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=87123. 
7. ^ ^{a b c d e} Cho, H; Orphanides G, Sun X, Yang X J, Ogryzko V, Lees E, Nakatani Y, Reinberg D (Sep. 1998). "A Human RNA Polymerase II Complex Containing Factors That Modify Chromatin Structure". Mol. Cell. Biol. (UNITED STATES) 18 (9): 5355–63. ISSN 0270-7306. PMC 109120. PMID 9710619. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=109120. 
8. ^ Yang, Fajun; DeBeaumont Rosalie, Zhou Sharleen, Näär Anders M (Feb. 2004). "The activator-recruited cofactor/Mediator coactivator subunit ARC92 is a functionally important target of the VP16 transcriptional activator". Proc. Natl. Acad. Sci. U.S.A. (United States) 101 (8): 2339–44. doi:10.1073/pnas.0308676100. ISSN 0027-8424. PMC 356952. PMID 14983011. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=356952. 
9. ^ 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 (UNITED STATES) 89 (3): 357–64. doi:10.1016/S0092-8674(00)80216-0. ISSN 0092-8674. PMID 9150135. 
10. ^ Suñé, C; Hayashi T, Liu Y, Lane W S, Young R A, Garcia-Blanco M A (Oct. 1997). "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. (UNITED STATES) 17 (10): 6029–39. ISSN 0270-7306. PMC 232452. PMID 9315662. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=232452. 

Further reading

• Schultz SJ, Nigg EA (1994). "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. 4 (10): 821–30. PMID 8274451. 
• Rickert P, Seghezzi W, Shanahan F, et al. (1996). "Cyclin C/CDK8 is a novel CTD kinase associated with RNA polymerase II". Oncogene 12 (12): 2631–40. PMID 8700522. 
• Cujec TP, Cho H, Maldonado E, et al. (1997). "The human immunodeficiency virus transactivator Tat interacts with the RNA polymerase II holoenzyme". Mol. Cell. Biol. 17 (4): 1817–23. PMC 232028. PMID 9121429. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=232028. 
• Scully R, Anderson SF, Chao DM, et al. (1997). "BRCA1 is a component of the RNA polymerase II holoenzyme". Proc. Natl. Acad. Sci. U.S.A. 94 (11): 5605–10. doi:10.1073/pnas.94.11.5605. PMC 20825. PMID 9159119. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=20825. 
• Neish AS, Anderson SF, Schlegel BP, et al. (1998). "Factors associated with the mammalian RNA polymerase II holoenzyme". Nucleic Acids Res. 26 (3): 847–53. doi:10.1093/nar/26.3.847. PMC 147327. PMID 9443979. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=147327. 
• Cho H, Orphanides G, Sun X, et al. (1998). "A Human RNA Polymerase II Complex Containing Factors That Modify Chromatin Structure". Mol. Cell. Biol. 18 (9): 5355–63. PMC 109120. PMID 9710619. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=109120. 
• Sun X, Zhang Y, Cho H, et al. (1998). "NAT, a human complex containing Srb polypeptides that functions as a negative regulator of activated transcription". Mol. Cell 2 (2): 213–22. doi:10.1016/S1097-2765(00)80131-8. PMID 9734358. 
• Rickert P, Corden JL, Lees E (1999). "Cyclin C/CDK8 and cyclin H/CDK7/p36 are biochemically distinct CTD kinases". Oncogene 18 (4): 1093–102. doi:10.1038/sj.onc.1202399. PMID 10023686. 
• Gu W, Malik S, Ito M, et al. (1999). "A novel human SRB/MED-containing cofactor complex, SMCC, involved in transcription regulation". Mol. Cell 3 (1): 97–108. doi:10.1016/S1097-2765(00)80178-1. PMID 10024883. 
• Ito M, Yuan CX, Malik S, et al. (1999). "Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators". Mol. Cell 3 (3): 361–70. doi:10.1016/S1097-2765(00)80463-3. PMID 10198638. 
• Rachez C, Lemon BD, Suldan Z, et al. (1999). "Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex". Nature 398 (6730): 824–8. doi:10.1038/19783. PMID 10235266. 
• Akoulitchev S, Chuikov S, Reinberg D (2000). "TFIIH is negatively regulated by cdk8-containing mediator complexes". Nature 407 (6800): 102–6. doi:10.1038/35024111. PMID 10993082. 
• Ramanathan Y, Rajpara SM, Reza SM, et al. (2001). "Three RNA polymerase II carboxyl-terminal domain kinases display distinct substrate preferences". J. Biol. Chem. 276 (14): 10913–20. doi:10.1074/jbc.M010975200. PMID 11278802. 
• Wang G, Cantin GT, Stevens JL, Berk AJ (2001). "Characterization of Mediator Complexes from HeLa Cell Nuclear Extract". Mol. Cell. Biol. 21 (14): 4604–13. doi:10.1128/MCB.21.14.4604-4613.2001. PMC 87123. PMID 11416138. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=87123. 
• Di Pietro C, Rapisarda A, Bonaiuto C, et al. (2001). "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. 25 (3): 185–9. doi:10.1023/A:1018897624615. PMID 11441538. 
• Vogel L, Baratte B, Détivaud L, et al. (2002). "Molecular cloning and characterisation of p15(CDK-BP), a novel CDK-binding protein". Biochim. Biophys. Acta 1589 (2): 219–31. doi:10.1016/S0167-4889(02)00175-1. PMID 12007796. 
• Crowley TE, Kaine EM, Yoshida M, et al. (2003). "Reproductive cycle regulation of nuclear import, euchromatic localization, and association with components of Pol II mediator of a mammalian double-bromodomain protein". Mol. Endocrinol. 16 (8): 1727–37. doi:10.1210/me.2001-0353. PMID 12145330. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Sato S, Tomomori-Sato C, Banks CA, et al. (2003). "Identification of mammalian Mediator subunits with similarities to yeast Mediator subunits Srb5, Srb6, Med11, and Rox3". J. Biol. Chem. 278 (17): 15123–7. doi:10.1074/jbc.C300054200. PMID 12584197. 

External links

• MeSH CDK8+protein,+human

B bsyn: dna (repl, cycl, reco, repr) · tscr (fact, tcrg, nucl, rnat, rept, ptts) · tltn (risu, pttl, nexn) · dnab, rnab/runp · stru (domn, 1°, 2°, 3°, 4°)