Cyclin-dependent kinase 9

Details

Name
Cyclin-dependent kinase 9
Kind
protein
Synonyms
  • 2.7.11.22
  • 2.7.11.23
  • C-2K
  • CDC2L4
  • Cell division cycle 2-like protein kinase 4
  • Cell division protein kinase 9
  • Serine/threonine-protein kinase PITALRE
  • TAK
  • Tat-associated kinase complex catalytic subunit
Gene Name
CDK9
UniProtKB Entry
P50750Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0004331|Cyclin-dependent kinase 9
MAKQYDSVECPFCDEVSKYEKLAKIGQGTFGEVFKARHRKTGQKVALKKVLMENEKEGFP
ITALREIKILQLLKHENVVNLIEICRTKASPYNRCKGSIYLVFDFCEHDLAGLLSNVLVK
FTLSEIKRVMQMLLNGLYYIHRNKILHRDMKAANVLITRDGVLKLADFGLARAFSLAKNS
QPNRYTNRVVTLWYRPPELLLGERDYGPPIDLWGAGCIMAEMWTRSPIMQGNTEQHQLAL
ISQLCGSITPEVWPNVDNYELYEKLELVKGQKRKVKDRLKAYVRDPYALDLIDKLLVLDP
AQRIDSDDALNHDFFWSDPMPSDLKGMLSTHLTSMFEYLAPPRRKGSQITQQSTNQSRNP
ATTNQTEFERVF
Number of residues
372
Molecular Weight
42777.155
Theoretical pI
9.07
GO Classification
Functions
7SK snRNA binding / kinase activity / protein kinase binding / protein serine kinase activity / protein serine/threonine kinase activity / RNA polymerase II cis-regulatory region sequence-specific DNA binding / RNA polymerase II CTD heptapeptide repeat kinase activity / transcription coactivator binding / transcription elongation factor activity
Processes
cell population proliferation / negative regulation of protein localization to chromatin / nucleus localization / positive regulation by host of viral transcription / positive regulation of protein localization to chromatin / positive regulation of transcription by RNA polymerase II / positive regulation of transcription elongation by RNA polymerase II / regulation of cell cycle / regulation of mRNA 3'-end processing / regulation of muscle cell differentiation / transcription by RNA polymerase II / transcription elongation by RNA polymerase II / transcription elongation-coupled chromatin remodeling / transcription initiation at RNA polymerase II promoter
Components
cyclin/CDK positive transcription elongation factor complex / cytoplasmic ribonucleoprotein granule / nucleus / P-TEFb complex
General Function
Protein kinase involved in the regulation of transcription (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:20930849, PubMed:28426094, PubMed:29335245). Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:20930849, PubMed:28426094, PubMed:30134174). This complex is inactive when in the 7SK snRNP complex form (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:20930849, PubMed:28426094). Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR and the negative elongation factors DSIF and NELFE (PubMed:10912001, PubMed:11112772, PubMed:12037670, PubMed:20081228, PubMed:20980437, PubMed:21127351, PubMed:9857195). Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling) (PubMed:17956865, PubMed:18362169). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis (PubMed:10393184, PubMed:11112772). P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export (PubMed:15564463, PubMed:19575011, PubMed:19844166). Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3; integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing (PubMed:15564463, PubMed:19575011, PubMed:19844166). The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro (PubMed:21127351). Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage (PubMed:20493174). In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6 (PubMed:20493174). Promotes cardiac myocyte enlargement (PubMed:20081228). RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription (PubMed:21127351). AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect (PubMed:10912001, PubMed:11112772, PubMed:9857195). The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation (PubMed:12037670). Catalyzes phosphorylation of KAT5, promoting KAT5 recruitment to chromatin and histone acetyltransferase activity (PubMed:29335245)
Specific Function
7sk snrna binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0021677|Cyclin-dependent kinase 9 (CDK9)
ATGGCAAAGCAGTACGACTCGGTGGAGTGCCCTTTTTGTGATGAAGTTTCCAAATACGAG
AAGCTCGCCAAGATCGGCCAAGGCACCTTCGGGGAGGTGTTCAAGGCCAGGCACCGCAAG
ACCGGCCAGAAGGTGGCTCTGAAGAAGGTGCTGATGGAAAACGAGAAGGAGGGGTTCCCC
ATTACAGCCTTGCGGGAGATCAAGATCCTTCAGCTTCTAAAACACGAGAATGTGGTCAAC
TTGATTGAGATTTGTCGAACCAAAGCTTCCCCCTATAACCGCTGCAAGGGTAGTATATAC
CTGGTGTTCGACTTCTGCGAGCATGACCTTGCTGGGCTGTTGAGCAATGTTTTGGTCAAG
TTCACGCTGTCTGAGATCAAGAGGGTGATGCAGATGCTGCTTAACGGCCTCTACTACATC
CACAGAAACAAGATCCTGCATAGGGACATGAAGGCTGCTAATGTGCTTATCACTCGTGAT
GGGGTCCTGAAGCTGGCAGACTTTGGGCTGGCCCGGGCCTTCAGCCTGGCCAAGAACAGC
CAGCCCAACCGCTACACCAACCGTGTGGTGACACTCTGGTACCGGCCCCCGGAGCTGTTG
CTCGGGGAGCGGGACTACGGCCCCCCCATTGACCTGTGGGGTGCTGGGTGCATCATGGCA
GAGATGTGGACCCGCAGCCCCATCATGCAGGGCAACACGGAGCAGCACCAACTCGCCCTC
ATCAGTCAGCTCTGCGGCTCCATCACCCCTGAGGTGTGGCCAAACGTGGACAACTATGAG
CTGTACGAAAAGCTGGAGCTGGTCAAGGGCCAGAAGCGGAAGGTGAAGGACAGGCTGAAG
GCCTATGTGCGTGACCCATACGCACTGGACCTCATCGACAAGCTGCTGGTGCTGGACCCT
GCCCAGCGCATCGACAGCGATGACGCCCTCAACCACGACTTCTTCTGGTCCGACCCCATG
CCCTCCGACCTCAAGGGCATGCTCTCCACCCACCTGACGTCCATGTTCGAGTACTTGGCA
CCACCGCGCCGGAAGGGCAGCCAGATCACCCAGCAGTCCACCAACCAGAGTCGCAATCCC
GCCACCACCAACCAGACGGAGTTTGAGCGCGTCTTCTGA
Chromosome Location
9
Locus
9q34.11
External Identifiers
ResourceLink
UniProtKB IDP50750
UniProtKB Entry NameCDK9_HUMAN
GenBank Protein ID493130
GenBank Gene IDL25676
GeneCard IDCDK9
GenAtlas IDCDK9
HGNC IDHGNC:1780
PDB ID(s)3BLH, 3BLQ, 3BLR, 3LQ5, 3MI9, 3MIA, 3MY1, 3TN8, 3TNH, 3TNI, 4BCF, 4BCG, 4BCH, 4BCI, 4BCJ, 4EC8, 4EC9, 4IMY, 4OGR, 4OR5, 5L1Z, 6CYT, 6GZH, 6W9E, 6Z45, 7NWK, 8I0L, 8K5R
KEGG IDhsa:1025
IUPHAR/Guide To Pharmacology ID1981
NCBI Gene ID1025
General References
  1. Grana X, De Luca A, Sang N, Fu Y, Claudio PP, Rosenblatt J, Morgan DO, Giordano A: PITALRE, a nuclear CDC2-related protein kinase that phosphorylates the retinoblastoma protein in vitro. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3834-8. [Article]
  2. Best JL, Presky DH, Swerlick RA, Burns DK, Chu W: Cloning of a full-length cDNA sequence encoding a cdc2-related protein kinase from human endothelial cells. Biochem Biophys Res Commun. 1995 Mar 17;208(2):562-8. [Article]
  3. Liu H, Rice AP: Genomic organization and characterization of promoter function of the human CDK9 gene. Gene. 2000 Jul 11;252(1-2):51-9. [Article]
  4. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. [Article]
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  6. Wei P, Garber ME, Fang SM, Fischer WH, Jones KA: A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA. Cell. 1998 Feb 20;92(4):451-62. [Article]
  7. Wada T, Takagi T, Yamaguchi Y, Watanabe D, Handa H: Evidence that P-TEFb alleviates the negative effect of DSIF on RNA polymerase II-dependent transcription in vitro. EMBO J. 1998 Dec 15;17(24):7395-403. [Article]
  8. Peng J, Zhu Y, Milton JT, Price DH: Identification of multiple cyclin subunits of human P-TEFb. Genes Dev. 1998 Mar 1;12(5):755-62. [Article]
  9. Parada CA, Roeder RG: A novel RNA polymerase II-containing complex potentiates Tat-enhanced HIV-1 transcription. EMBO J. 1999 Jul 1;18(13):3688-701. [Article]
  10. Fu TJ, Peng J, Lee G, Price DH, Flores O: Cyclin K functions as a CDK9 regulatory subunit and participates in RNA polymerase II transcription. J Biol Chem. 1999 Dec 3;274(49):34527-30. [Article]
  11. Wada T, Orphanides G, Hasegawa J, Kim DK, Shima D, Yamaguchi Y, Fukuda A, Hisatake K, Oh S, Reinberg D, Handa H: FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and reveals functional differences between P-TEFb and TFIIH. Mol Cell. 2000 Jun;5(6):1067-72. [Article]
  12. Ivanov D, Kwak YT, Guo J, Gaynor RB: Domains in the SPT5 protein that modulate its transcriptional regulatory properties. Mol Cell Biol. 2000 May;20(9):2970-83. [Article]
  13. Garber ME, Mayall TP, Suess EM, Meisenhelder J, Thompson NE, Jones KA: CDK9 autophosphorylation regulates high-affinity binding of the human immunodeficiency virus type 1 tat-P-TEFb complex to TAR RNA. Mol Cell Biol. 2000 Sep;20(18):6958-69. [Article]
  14. Kim JB, Sharp PA: Positive transcription elongation factor B phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase. J Biol Chem. 2001 Apr 13;276(15):12317-23. Epub 2001 Jan 5. [Article]
  15. Ping YH, Rana TM: DSIF and NELF interact with RNA polymerase II elongation complex and HIV-1 Tat stimulates P-TEFb-mediated phosphorylation of RNA polymerase II and DSIF during transcription elongation. J Biol Chem. 2001 Apr 20;276(16):12951-8. Epub 2000 Dec 8. [Article]
  16. Lavoie SB, Albert AL, Handa H, Vincent M, Bensaude O: The peptidyl-prolyl isomerase Pin1 interacts with hSpt5 phosphorylated by Cdk9. J Mol Biol. 2001 Sep 28;312(4):675-85. [Article]
  17. Lin X, Taube R, Fujinaga K, Peterlin BM: P-TEFb containing cyclin K and Cdk9 can activate transcription via RNA. J Biol Chem. 2002 May 10;277(19):16873-8. Epub 2002 Mar 7. [Article]
  18. Estable MC, Naghavi MH, Kato H, Xiao H, Qin J, Vahlne A, Roeder RG: MCEF, the newest member of the AF4 family of transcription factors involved in leukemia, is a positive transcription elongation factor-b-associated protein. J Biomed Sci. 2002 May-Jun;9(3):234-45. [Article]
  19. Napolitano G, Licciardo P, Carbone R, Majello B, Lania L: CDK9 has the intrinsic property to shuttle between nucleus and cytoplasm, and enhanced expression of cyclin T1 promotes its nuclear localization. J Cell Physiol. 2002 Aug;192(2):209-15. [Article]
  20. Bourgeois CF, Kim YK, Churcher MJ, West MJ, Karn J: Spt5 cooperates with human immunodeficiency virus type 1 Tat by preventing premature RNA release at terminator sequences. Mol Cell Biol. 2002 Feb;22(4):1079-93. [Article]
  21. Simone C, Stiegler P, Bagella L, Pucci B, Bellan C, De Falco G, De Luca A, Guanti G, Puri PL, Giordano A: Activation of MyoD-dependent transcription by cdk9/cyclin T2. Oncogene. 2002 Jun 13;21(26):4137-48. [Article]
  22. Kwak YT, Guo J, Prajapati S, Park KJ, Surabhi RM, Miller B, Gehrig P, Gaynor RB: Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties. Mol Cell. 2003 Apr;11(4):1055-66. [Article]
  23. Zhou M, Deng L, Lacoste V, Park HU, Pumfery A, Kashanchi F, Brady JN, Kumar A: Coordination of transcription factor phosphorylation and histone methylation by the P-TEFb kinase during human immunodeficiency virus type 1 transcription. J Virol. 2004 Dec;78(24):13522-33. [Article]
  24. Fujinaga K, Irwin D, Huang Y, Taube R, Kurosu T, Peterlin BM: Dynamics of human immunodeficiency virus transcription: P-TEFb phosphorylates RD and dissociates negative effectors from the transactivation response element. Mol Cell Biol. 2004 Jan;24(2):787-95. [Article]
  25. Li Q, Price JP, Byers SA, Cheng D, Peng J, Price DH: Analysis of the large inactive P-TEFb complex indicates that it contains one 7SK molecule, a dimer of HEXIM1 or HEXIM2, and two P-TEFb molecules containing Cdk9 phosphorylated at threonine 186. J Biol Chem. 2005 Aug 5;280(31):28819-26. Epub 2005 Jun 17. [Article]
  26. Jang MK, Mochizuki K, Zhou M, Jeong HS, Brady JN, Ozato K: The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription. Mol Cell. 2005 Aug 19;19(4):523-34. [Article]
  27. Yang Z, Yik JH, Chen R, He N, Jang MK, Ozato K, Zhou Q: Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4. Mol Cell. 2005 Aug 19;19(4):535-45. [Article]
  28. Hou T, Ray S, Brasier AR: The functional role of an interleukin 6-inducible CDK9.STAT3 complex in human gamma-fibrinogen gene expression. J Biol Chem. 2007 Dec 21;282(51):37091-102. Epub 2007 Oct 23. [Article]
  29. Jeronimo C, Forget D, Bouchard A, Li Q, Chua G, Poitras C, Therien C, Bergeron D, Bourassa S, Greenblatt J, Chabot B, Poirier GG, Hughes TR, Blanchette M, Price DH, Coulombe B: Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme. Mol Cell. 2007 Jul 20;27(2):262-74. [Article]
  30. Fu J, Yoon HG, Qin J, Wong J: Regulation of P-TEFb elongation complex activity by CDK9 acetylation. Mol Cell Biol. 2007 Jul;27(13):4641-51. Epub 2007 Apr 23. [Article]
  31. Chen R, Liu M, Li H, Xue Y, Ramey WN, He N, Ai N, Luo H, Zhu Y, Zhou N, Zhou Q: PP2B and PP1alpha cooperatively disrupt 7SK snRNP to release P-TEFb for transcription in response to Ca2+ signaling. Genes Dev. 2008 May 15;22(10):1356-68. doi: 10.1101/gad.1636008. [Article]
  32. Wang Y, Dow EC, Liang YY, Ramakrishnan R, Liu H, Sung TL, Lin X, Rice AP: Phosphatase PPM1A regulates phosphorylation of Thr-186 in the Cdk9 T-loop. J Biol Chem. 2008 Nov 28;283(48):33578-84. doi: 10.1074/jbc.M807495200. Epub 2008 Oct 1. [Article]
  33. He N, Jahchan NS, Hong E, Li Q, Bayfield MA, Maraia RJ, Luo K, Zhou Q: A La-related protein modulates 7SK snRNP integrity to suppress P-TEFb-dependent transcriptional elongation and tumorigenesis. Mol Cell. 2008 Mar 14;29(5):588-99. doi: 10.1016/j.molcel.2008.01.003. Epub 2008 Jan 31. [Article]
  34. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
  35. Sabo A, Lusic M, Cereseto A, Giacca M: Acetylation of conserved lysines in the catalytic core of cyclin-dependent kinase 9 inhibits kinase activity and regulates transcription. Mol Cell Biol. 2008 Apr;28(7):2201-12. doi: 10.1128/MCB.01557-07. Epub 2008 Feb 4. [Article]
  36. Nowak DE, Tian B, Jamaluddin M, Boldogh I, Vergara LA, Choudhary S, Brasier AR: RelA Ser276 phosphorylation is required for activation of a subset of NF-kappaB-dependent genes by recruiting cyclin-dependent kinase 9/cyclin T1 complexes. Mol Cell Biol. 2008 Jun;28(11):3623-38. doi: 10.1128/MCB.01152-07. Epub 2008 Mar 24. [Article]
  37. Pirngruber J, Shchebet A, Johnsen SA: Insights into the function of the human P-TEFb component CDK9 in the regulation of chromatin modifications and co-transcriptional mRNA processing. Cell Cycle. 2009 Nov 15;8(22):3636-42. Epub 2009 Nov 24. [Article]
  38. Pirngruber J, Shchebet A, Schreiber L, Shema E, Minsky N, Chapman RD, Eick D, Aylon Y, Oren M, Johnsen SA: CDK9 directs H2B monoubiquitination and controls replication-dependent histone mRNA 3'-end processing. EMBO Rep. 2009 Aug;10(8):894-900. doi: 10.1038/embor.2009.108. Epub 2009 Jul 3. [Article]
  39. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [Article]
  40. Liu H, Herrmann CH, Chiang K, Sung TL, Moon SH, Donehower LA, Rice AP: 55K isoform of CDK9 associates with Ku70 and is involved in DNA repair. Biochem Biophys Res Commun. 2010 Jun 25;397(2):245-50. doi: 10.1016/j.bbrc.2010.05.092. Epub 2010 May 20. [Article]
  41. Yu DS, Zhao R, Hsu EL, Cayer J, Ye F, Guo Y, Shyr Y, Cortez D: Cyclin-dependent kinase 9-cyclin K functions in the replication stress response. EMBO Rep. 2010 Nov;11(11):876-82. doi: 10.1038/embor.2010.153. Epub 2010 Oct 8. [Article]
  42. Sunagawa Y, Morimoto T, Takaya T, Kaichi S, Wada H, Kawamura T, Fujita M, Shimatsu A, Kita T, Hasegawa K: Cyclin-dependent kinase-9 is a component of the p300/GATA4 complex required for phenylephrine-induced hypertrophy in cardiomyocytes. J Biol Chem. 2010 Mar 26;285(13):9556-68. doi: 10.1074/jbc.M109.070458. Epub 2010 Jan 17. [Article]
  43. He N, Liu M, Hsu J, Xue Y, Chou S, Burlingame A, Krogan NJ, Alber T, Zhou Q: HIV-1 Tat and host AFF4 recruit two transcription elongation factors into a bifunctional complex for coordinated activation of HIV-1 transcription. Mol Cell. 2010 May 14;38(3):428-38. doi: 10.1016/j.molcel.2010.04.013. [Article]
  44. Lin C, Smith ER, Takahashi H, Lai KC, Martin-Brown S, Florens L, Washburn MP, Conaway JW, Conaway RC, Shilatifard A: AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia. Mol Cell. 2010 Feb 12;37(3):429-37. doi: 10.1016/j.molcel.2010.01.026. [Article]
  45. Gordon V, Bhadel S, Wunderlich W, Zhang J, Ficarro SB, Mollah SA, Shabanowitz J, Hunt DF, Xenarios I, Hahn WC, Conaway M, Carey MF, Gioeli D: CDK9 regulates AR promoter selectivity and cell growth through serine 81 phosphorylation. Mol Endocrinol. 2010 Dec;24(12):2267-80. doi: 10.1210/me.2010-0238. Epub 2010 Oct 27. [Article]
  46. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  47. Smith ER, Lin C, Garrett AS, Thornton J, Mohaghegh N, Hu D, Jackson J, Saraf A, Swanson SK, Seidel C, Florens L, Washburn MP, Eissenberg JC, Shilatifard A: The little elongation complex regulates small nuclear RNA transcription. Mol Cell. 2011 Dec 23;44(6):954-65. doi: 10.1016/j.molcel.2011.12.008. [Article]
  48. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [Article]
  49. Liu X, Shi S, Lam F, Pepper C, Fischer PM, Wang S: CDKI-71, a novel CDK9 inhibitor, is preferentially cytotoxic to cancer cells compared to flavopiridol. Int J Cancer. 2012 Mar 1;130(5):1216-26. doi: 10.1002/ijc.26127. Epub 2011 Jun 21. [Article]
  50. Cojocaru M, Bouchard A, Cloutier P, Cooper JJ, Varzavand K, Price DH, Coulombe B: Transcription factor IIS cooperates with the E3 ligase UBR5 to ubiquitinate the CDK9 subunit of the positive transcription elongation factor B. J Biol Chem. 2011 Feb 18;286(7):5012-22. doi: 10.1074/jbc.M110.176628. Epub 2010 Dec 2. [Article]
  51. Ramakrishnan R, Rice AP: Cdk9 T-loop phosphorylation is regulated by the calcium signaling pathway. J Cell Physiol. 2012 Feb;227(2):609-17. doi: 10.1002/jcp.22760. [Article]
  52. Ammosova T, Obukhov Y, Kotelkin A, Breuer D, Beullens M, Gordeuk VR, Bollen M, Nekhai S: Protein phosphatase-1 activates CDK9 by dephosphorylating Ser175. PLoS One. 2011 Apr 21;6(4):e18985. doi: 10.1371/journal.pone.0018985. [Article]
  53. Peterlin BM, Price DH: Controlling the elongation phase of transcription with P-TEFb. Mol Cell. 2006 Aug 4;23(3):297-305. [Article]
  54. Brasier AR: Expanding role of cyclin dependent kinases in cytokine inducible gene expression. Cell Cycle. 2008 Sep 1;7(17):2661-6. Epub 2008 Sep 12. [Article]
  55. Romano G, Giordano A: Role of the cyclin-dependent kinase 9-related pathway in mammalian gene expression and human diseases. Cell Cycle. 2008 Dec;7(23):3664-8. Epub 2008 Dec 4. [Article]
  56. Wang S, Fischer PM: Cyclin-dependent kinase 9: a key transcriptional regulator and potential drug target in oncology, virology and cardiology. Trends Pharmacol Sci. 2008 Jun;29(6):302-13. doi: 10.1016/j.tips.2008.03.003. Epub 2008 Apr 16. [Article]
  57. Malumbres M, Barbacid M: Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009 Mar;9(3):153-66. doi: 10.1038/nrc2602. [Article]
  58. Krystof V, Chamrad I, Jorda R, Kohoutek J: Pharmacological targeting of CDK9 in cardiac hypertrophy. Med Res Rev. 2010 Jul;30(4):646-66. doi: 10.1002/med.20172. [Article]
  59. Yu DS, Cortez D: A role for CDK9-cyclin K in maintaining genome integrity. Cell Cycle. 2011 Jan 1;10(1):28-32. Epub 2011 Jan 1. [Article]
  60. Guo L, Wu WJ, Liu LD, Wang LC, Zhang Y, Wu LQ, Guan Y, Li QH: Herpes simplex virus 1 ICP22 inhibits the transcription of viral gene promoters by binding to and blocking the recruitment of P-TEFb. PLoS One. 2012;7(9):e45749. doi: 10.1371/journal.pone.0045749. Epub 2012 Sep 24. [Article]
  61. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  62. Tahirov TH, Babayeva ND, Varzavand K, Cooper JJ, Sedore SC, Price DH: Crystal structure of HIV-1 Tat complexed with human P-TEFb. Nature. 2010 Jun 10;465(7299):747-51. doi: 10.1038/nature09131. [Article]
  63. Baumli S, Lolli G, Lowe ED, Troiani S, Rusconi L, Bullock AN, Debreczeni JE, Knapp S, Johnson LN: The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol and regulation by phosphorylation. EMBO J. 2008 Jul 9;27(13):1907-18. doi: 10.1038/emboj.2008.121. Epub 2008 Jun 19. [Article]
  64. Baumli S, Endicott JA, Johnson LN: Halogen bonds form the basis for selective P-TEFb inhibition by DRB. Chem Biol. 2010 Sep 24;17(9):931-6. doi: 10.1016/j.chembiol.2010.07.012. [Article]
  65. Bettayeb K, Baunbaek D, Delehouze C, Loaec N, Hole AJ, Baumli S, Endicott JA, Douc-Rasy S, Benard J, Oumata N, Galons H, Meijer L: CDK Inhibitors Roscovitine and CR8 Trigger Mcl-1 Down-Regulation and Apoptotic Cell Death in Neuroblastoma Cells. Genes Cancer. 2010 Apr;1(4):369-80. doi: 10.1177/1947601910369817. [Article]
  66. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Alvocidibexperimental, investigationalyestargetinhibitorDetails
SeliciclibinvestigationalunknowntargetDetails
Trilaciclibapproved, investigationalnotargetinhibitorDetails
ZotiraciclibinvestigationalunknowntargetinhibitorDetails
(7S)-2-(2-aminopyrimidin-4-yl)-7-(2-fluoroethyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-oneexperimentalyestargetinhibitorDetails
4-(4-propoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amineexperimentalyestargetinhibitorDetails
4-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amineexperimentalyestargetinhibitorDetails
DinaciclibinvestigationalyestargetinhibitorDetails
SNS-032investigationalyestargetinhibitorDetails
ZemirciclibinvestigationalyestargetinhibitorDetails
CYC-065investigationalyestargetinhibitorDetails
TP-1287investigationalyestargetinhibitorDetails