CDK9

Cyclin-dependent kinase 9
Rendering based on PDB 1PF6.
Available structures PDB 1PF6, 3BLH, 3BLQ, 3BLR, 3MI9, 3MIA, 3MY1
Identifiers
Symbols	CDK9; C-2k; CDC2L4; CTK1; PITALRE; TAK
External IDs	OMIM: 603251 MGI: 1328368 HomoloGene: 55566 GeneCards: CDK9 Gene
Gene Ontology Molecular function • nucleotide binding • DNA binding • protein kinase activity • cyclin-dependent protein kinase activity • protein binding • ATP binding • RNA polymerase II carboxy-terminal domain kinase activity • kinase activity • snRNA binding Cellular component • nucleus • nucleoplasm • nucleoplasm • nucleolus • transcription elongation factor complex • intracellular membrane-bounded organelle Biological process • regulation of transcription, DNA-dependent • transcription from RNA polymerase II promoter • transcription initiation from RNA polymerase II promoter • transcription elongation from RNA polymerase II promoter • protein phosphorylation • protein phosphorylation • cell cycle • cell proliferation • gene expression • viral reproduction • phosphorylation • positive regulation of viral transcription Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1025	107951
Ensembl	ENSG00000136807	ENSMUSG00000009555
UniProt	P50750	Q99J95
RefSeq (mRNA)	NM_001261.3	NM_130860.3
RefSeq (protein)	NP_001252.1	NP_570930.1
Location (UCSC)	Chr 9: 130.55 – 130.55 Mb	Chr 2: 32.56 – 32.57 Mb
PubMed search	[1]	[2]

CDK9 or cyclin-dependent kinase 9 is a cyclin-dependent kinase associated with P-TEFb. 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 S. cerevisiae cdc28, and S. pombe cdc2, and known as important cell cycle regulators. This kinase was found to be a component of the multiprotein complex TAK/P-TEFb, which is an elongation factor for RNA polymerase II-directed transcription and functions by phosphorylating the C-terminal domain of the largest subunit of RNA polymerase II. This protein forms a complex with and is regulated by its regulatory subunit cyclin T or cyclin K. HIV-1 Tat protein was found to interact with this protein and cyclin T, which suggested a possible involvement of this protein in AIDS. ^[1] CDK9 is also known to associate with other proteins such as TRAF2, and be involved in differentiation of skeletal muscle. ^[2]

Interactions

CDK9 has been shown to interact with Cyclin K,^[3] Cyclin T2,^[4] RELA,^[5] Cyclin T1,^{[6][7][8][9][10][11][3][4][12]} Retinoblastoma protein,^[13] Androgen receptor,^[14] SKP1A,^[10] MYBL2,^[11] CDC34^[10] and SUPT5H.^[12]

References

1. ^ "Entrez Gene: CDK9 cyclin-dependent kinase 9 (CDC2-related kinase)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1025. 
2. ^ MacLachlan TK, Sang N, De Luca A, Puri PL, Levrero M, Giordano A., et al. (1998). "Binding of CDK9 to TRAF2.". J. Cell. Biochem. 71 (4): 467–78. doi:10.1002/(SICI)1097-4644(19981215)71:4<467::AID-JCB2>3.0.CO;2-G. PMID 9827693. 
3. ^ ^{a b} Fu, T J; Peng J, Lee G, Price D H, Flores O (Dec. 1999). "Cyclin K functions as a CDK9 regulatory subunit and participates in RNA polymerase II transcription". J. Biol. Chem. (UNITED STATES) 274 (49): 34527–30. doi:10.1074/jbc.274.49.34527. ISSN 0021-9258. PMID 10574912. 
4. ^ ^{a b} Peng, J; Zhu Y, Milton J T, Price D H (Mar. 1998). "Identification of multiple cyclin subunits of human P-TEFb". Genes Dev. (UNITED STATES) 12 (5): 755–62. doi:10.1101/gad.12.5.755. ISSN 0890-9369. PMC 316581. PMID 9499409. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=316581. 
5. ^ Amini, Shohreh; Clavo Anaira, Nadraga Yuri, Giordano Antonio, Khalili Kamel, Sawaya Bassel E (Aug. 2002). "Interplay between cdk9 and NF-kappaB factors determines the level of HIV-1 gene transcription in astrocytic cells". Oncogene (England) 21 (37): 5797–803. doi:10.1038/sj.onc.1205754. ISSN 0950-9232. PMID 12173051. 
6. ^ Cabart, Pavel; Chew Helen K, Murphy Shona (Jul. 2004). "BRCA1 cooperates with NUFIP and P-TEFb to activate transcription by RNA polymerase II". Oncogene (England) 23 (31): 5316–29. doi:10.1038/sj.onc.1207684. ISSN 0950-9232. PMID 15107825. 
7. ^ Young, Tara M; Wang Qi, Pe'ery Tsafi, Mathews Michael B (Sep. 2003). "The human I-mfa domain-containing protein, HIC, interacts with cyclin T1 and modulates P-TEFb-dependent transcription". Mol. Cell. Biol. (United States) 23 (18): 6373–84. doi:10.1128/MCB.23.18.6373-6384.2003. ISSN 0270-7306. PMC 193714. PMID 12944466. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=193714. 
8. ^ Michels, Annemieke A; Nguyen Van Trung, Fraldi Alessandro, Labas Valérie, Edwards Mia, Bonnet François, Lania Luigi, Bensaude Olivier (Jul. 2003). "MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner". Mol. Cell. Biol. (United States) 23 (14): 4859–69. doi:10.1128/MCB.23.14.4859-4869.2003. ISSN 0270-7306. PMC 162212. PMID 12832472. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=162212. 
9. ^ Hoque, Mainul; Young Tara M, Lee Chee-Gun, Serrero Ginette, Mathews Michael B, Pe'ery Tsafi (Mar. 2003). "The growth factor granulin interacts with cyclin T1 and modulates P-TEFb-dependent transcription". Mol. Cell. Biol. (United States) 23 (5): 1688–702. doi:10.1128/MCB.23.5.1688-1702.2003. ISSN 0270-7306. PMC 151712. PMID 12588988. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=151712. 
10. ^ ^{a b c} Kiernan, R E; Emiliani S, Nakayama K, Castro A, Labbé J C, Lorca T, Nakayama Ki K, Benkirane M (Dec. 2001). "Interaction between cyclin T1 and SCF(SKP2) targets CDK9 for ubiquitination and degradation by the proteasome". Mol. Cell. Biol. (United States) 21 (23): 7956–70. doi:10.1128/MCB.21.23.7956-7970.2001. ISSN 0270-7306. PMC 99964. PMID 11689688. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=99964. 
11. ^ ^{a b} De Falco, G; Bagella L, Claudio P P, De Luca A, Fu Y, Calabretta B, Sala A, Giordano A (Jan. 2000). "Physical interaction between CDK9 and B-Myb results in suppression of B-Myb gene autoregulation". Oncogene (ENGLAND) 19 (3): 373–9. doi:10.1038/sj.onc.1203305. ISSN 0950-9232. PMID 10656684. 
12. ^ ^{a b} Garber, M E; Mayall T P, Suess E M, Meisenhelder J, Thompson N E, Jones K A (Sep. 2000). "CDK9 autophosphorylation regulates high-affinity binding of the human immunodeficiency virus type 1 tat-P-TEFb complex to TAR RNA". Mol. Cell. Biol. (UNITED STATES) 20 (18): 6958–69. doi:10.1128/MCB.20.18.6958-6969.2000. ISSN 0270-7306. PMC 88771. PMID 10958691. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=88771. 
13. ^ Simone, Cristiano; Bagella Luigi, Bellan Cristiana, Giordano Antonio (Jun. 2002). "Physical interaction between pRb and cdk9/cyclinT2 complex". Oncogene (England) 21 (26): 4158–65. doi:10.1038/sj.onc.1205511. ISSN 0950-9232. PMID 12037672. 
14. ^ Lee, D K; Duan H O, Chang C (Mar. 2001). "Androgen receptor interacts with the positive elongation factor P-TEFb and enhances the efficiency of transcriptional elongation". J. Biol. Chem. (United States) 276 (13): 9978–84. doi:10.1074/jbc.M002285200. ISSN 0021-9258. PMID 11266437. 

Further reading

• Jeang KT (1998). "Tat, Tat-associated kinase, and transcription.". J. Biomed. Sci. 5 (1): 24–7. doi:10.1007/BF02253352. PMID 9570510. 
• Yankulov K, Bentley D (1998). "Transcriptional control: Tat cofactors and transcriptional elongation.". Curr. Biol. 8 (13): R447–9. doi:10.1016/S0960-9822(98)70289-1. PMID 9651670. 
• Romano G, Kasten M, De Falco G, et al. (2000). "Regulatory functions of Cdk9 and of cyclin T1 in HIV tat transactivation pathway gene expression.". J. Cell. Biochem. 75 (3): 357–68. doi:10.1002/(SICI)1097-4644(19991201)75:3<357::AID-JCB1>3.0.CO;2-K. PMID 10536359. 
• Marcello A, Zoppé M, Giacca M (2002). "Multiple modes of transcriptional regulation by the HIV-1 Tat transactivator.". IUBMB Life 51 (3): 175–81. doi:10.1080/152165401753544241. PMID 11547919. 
• Huigen MC, Kamp W, Nottet HS (2004). "Multiple effects of HIV-1 trans-activator protein on the pathogenesis of HIV-1 infection.". Eur. J. Clin. Invest. 34 (1): 57–66. doi:10.1111/j.1365-2362.2004.01282.x. PMID 14984439. 
• Rice AP, Herrmann CH (2004). "Regulation of TAK/P-TEFb in CD4+ T lymphocytes and macrophages.". Curr. HIV Res. 1 (4): 395–404. doi:10.2174/1570162033485159. PMID 15049426. 
• Minghetti L, Visentin S, Patrizio M, et al. (2004). "Multiple actions of the human immunodeficiency virus type-1 Tat protein on microglial cell functions.". Neurochem. Res. 29 (5): 965–78. doi:10.1023/B:NERE.0000021241.90133.89. PMID 15139295. 
• Liou LY, Herrmann CH, Rice AP (2005). "HIV-1 infection and regulation of Tat function in macrophages.". Int. J. Biochem. Cell Biol. 36 (9): 1767–75. doi:10.1016/j.biocel.2004.02.018. PMID 15183343. 
• Pugliese A, Vidotto V, Beltramo T, et al. (2005). "A review of HIV-1 Tat protein biological effects.". Cell Biochem. Funct. 23 (4): 223–7. doi:10.1002/cbf.1147. PMID 15473004. 
• Bannwarth S, Gatignol A (2005). "HIV-1 TAR RNA: the target of molecular interactions between the virus and its host.". Curr. HIV Res. 3 (1): 61–71. doi:10.2174/1570162052772924. PMID 15638724. 
• Gibellini D, Vitone F, Schiavone P, Re MC (2005). "HIV-1 tat protein and cell proliferation and survival: a brief review.". New Microbiol. 28 (2): 95–109. PMID 16035254. 
• Peruzzi F (2006). "The multiple functions of HIV-1 Tat: proliferation versus apoptosis.". Front. Biosci. 11: 708–17. doi:10.2741/1829. PMID 16146763. 

External links

• MeSH Cyclin-Dependent+Kinase+9
• Drosophila Cyclin dependent kinase 9 - The Interactive Fly

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°)