cdk9

Summary

Gene Symbol: cdk9
Description: cyclin dependent kinase 9
Alias: C-2k, CDC2L4, CTK1, PITALRE, TAK, cyclin-dependent kinase 9, CDC2-related kinase, cell division cycle 2-like protein kinase 4, cell division protein kinase 9, serine/threonine protein kinase PITALRE, tat-associated kinase complex catalytic subunit
Species: human
Products:     cdk9

Top Publications

  1. Tian B, Zhao Y, Kalita M, Edeh C, Paessler S, Casola A, et al. CDK9-dependent transcriptional elongation in the innate interferon-stimulated gene response to respiratory syncytial virus infection in airway epithelial cells. J Virol. 2013;87:7075-92 pubmed publisher
    ..ISG expression was mediated by the recruitment of IRF3, CDK9, polymerase II (Pol II), and phospho-Ser(2) carboxy-terminal domain (CTD) Pol II to the IFN-stimulated response ..
  2. Yang X, Herrmann C, Rice A. The human immunodeficiency virus Tat proteins specifically associate with TAK in vivo and require the carboxyl-terminal domain of RNA polymerase II for function. J Virol. 1996;70:4576-84 pubmed
    ..that the activation domains of these proteins specifically interact in vitro with a cellular protein kinase named TAK. In vitro, TAK phosphorylates the Tat-2 but not the Tat-1 protein, a 42-kDa polypeptide of unknown identity, and ..
  3. Easley R, Van Duyne R, Coley W, Guendel I, Dadgar S, Kehn Hall K, et al. Chromatin dynamics associated with HIV-1 Tat-activated transcription. Biochim Biophys Acta. 2010;1799:275-85 pubmed publisher
    ..Finally, we cover recent literature on viral microRNAs which have been shown to alter chromatin structure by inducing methylation or even by remodeling nucleosomes. ..
  4. Dow E, Liu H, Rice A. T-loop phosphorylated Cdk9 localizes to nuclear speckle domains which may serve as sites of active P-TEFb function and exchange between the Brd4 and 7SK/HEXIM1 regulatory complexes. J Cell Physiol. 2010;224:84-93 pubmed publisher
    ..Core P-TEFb is comprised of Cdk9 and a cyclin regulatory subunit, with Cyclin T1 being the predominant Cdk9-associated cyclin...
  5. Molle D, Maiuri P, Boireau S, Bertrand E, Knezevich A, Marcello A, et al. A real-time view of the TAR:Tat:P-TEFb complex at HIV-1 transcription sites. Retrovirology. 2007;4:36 pubmed
    ..We found that in the presence of Tat, Cdk9 remained bound to nascent HIV-1 RNAs for 71s...
  6. Krueger B, Jeronimo C, Roy B, Bouchard A, Barrandon C, Byers S, et al. LARP7 is a stable component of the 7SK snRNP while P-TEFb, HEXIM1 and hnRNP A1 are reversibly associated. Nucleic Acids Res. 2008;36:2219-29 pubmed publisher
    ..Our studies have identified LARP7 as a 7SK-binding protein and suggest that free P-TEFb levels are determined by a balance between release from the large form and reduction of total P-TEFb. ..
  7. Marcello A, Ferrari A, Pellegrini V, Pegoraro G, Lusic M, Beltram F, et al. Recruitment of human cyclin T1 to nuclear bodies through direct interaction with the PML protein. EMBO J. 2003;22:2156-66 pubmed
    Human cyclin T1, the cyclin partner of Cdk9 kinase in the positive transcription elongation factor b (P-TEFb), is an essential cellular cofactor that is recruited by the human immunodeficiency virus type 1 (HIV-1) Tat transactivator to ..
  8. Tahirov T, Babayeva N, Varzavand K, Cooper J, Sedore S, Price D. Crystal structure of HIV-1 Tat complexed with human P-TEFb. Nature. 2010;465:747-51 pubmed publisher
    ..Here we describe the crystal structure of the Tat.P-TEFb complex containing HIV-1 Tat, human Cdk9 (also known as CDK9), and human cyclin T1 (also known as CCNT1)...
  9. Kaehlcke K, Dorr A, Hetzer Egger C, Kiermer V, Henklein P, Schnoelzer M, et al. Acetylation of Tat defines a cyclinT1-independent step in HIV transactivation. Mol Cell. 2003;12:167-76 pubmed
    ..We propose that Tat acetylation may help in dissociating the Tat cofactor CyclinT1 from TAR RNA and serve to transfer Tat onto the elongating RNA polymerase II. ..

More Information

Publications144 found, 100 shown here

  1. Rice A, Herrmann C. Regulation of TAK/P-TEFb in CD4+ T lymphocytes and macrophages. Curr HIV Res. 2003;1:395-404 pubmed
    ..is essential for HIV replication and requires a cellular protein kinase activity termed TAK/P-TEFb, composed of CDK9 and cyclin T1, for its transactivation function...
  2. Montanuy I, Torremocha R, Hernández Munain C, Suñé C. Promoter influences transcription elongation: TATA-box element mediates the assembly of processive transcription complexes responsive to cyclin-dependent kinase 9. J Biol Chem. 2008;283:7368-78 pubmed publisher
    ..We determined that cyclin-dependent kinase 9 (CDK9), the kinase subunit of positive transcription elongation factor b (P-TEFb) complex, regulates transcriptional ..
  3. Romani B, Engelbrecht S, Glashoff R. Functions of Tat: the versatile protein of human immunodeficiency virus type 1. J Gen Virol. 2010;91:1-12 pubmed publisher
    ..Due to its pivotal role in viral replication and in disease pathogenesis, Tat and the cellular pathways targeted by Tat are potential targets for new anti-HIV drugs. ..
  4. Yang Z, Zhu Q, Luo K, Zhou Q. The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription. Nature. 2001;414:317-22 pubmed
    The human positive transcription elongation factor P-TEFb, consisting of a CDK9/cyclin T1 heterodimer, functions as both a general and an HIV-1 Tat-specific transcription factor...
  5. Sedore S, Byers S, Biglione S, Price J, Maury W, Price D. Manipulation of P-TEFb control machinery by HIV: recruitment of P-TEFb from the large form by Tat and binding of HEXIM1 to TAR. Nucleic Acids Res. 2007;35:4347-58 pubmed
    ..This suggests that in the absence of Tat, HEXIM1 may bind to TAR and repress transcription elongation of the HIV LTR. ..
  6. Sano M, Schneider M. Cyclin-dependent kinase-9: an RNAPII kinase at the nexus of cardiac growth and death cascades. Circ Res. 2004;95:867-76 pubmed
    ..RNA polymerase II (RNAPII) is itself a substrate for two protein kinases-the cyclin-dependent kinases Cdk7 and Cdk9--that are activated by hypertrophic cues...
  7. Jadlowsky J, Nojima M, Okamoto T, Fujinaga K. Dominant negative mutant cyclin T1 proteins that inhibit HIV transcription by forming a kinase inactive complex with Tat. J Gen Virol. 2008;89:2783-7 pubmed publisher
    ..the inhibitory mechanism revealed that this mutant CycT1 interacted with Tat and the cyclin-dependent kinase 9 (Cdk9) subunit of P-TEFb, but failed to stimulate the Cdk9 kinase activity critical for elongation...
  8. Yik J, Chen R, Pezda A, Zhou Q. Compensatory contributions of HEXIM1 and HEXIM2 in maintaining the balance of active and inactive positive transcription elongation factor b complexes for control of transcription. J Biol Chem. 2005;280:16368-76 pubmed
    ..Our results demonstrate that there is a tightly regulated cellular process to maintain the balance between active and inactive P-TEFb complexes, which controls global transcription as well as cell growth and differentiation. ..
  9. Markert A, Grimm M, Martinez J, Wiesner J, Meyerhans A, Meyuhas O, et al. The La-related protein LARP7 is a component of the 7SK ribonucleoprotein and affects transcription of cellular and viral polymerase II genes. EMBO Rep. 2008;9:569-75 pubmed publisher
    ..Thus, LARP7 is a negative transcriptional regulator of polymerase II genes, acting by means of the 7SK RNP system. ..
  10. Garber M, Wei P, Jones K. HIV-1 Tat interacts with cyclin T1 to direct the P-TEFb CTD kinase complex to TAR RNA. Cold Spring Harb Symp Quant Biol. 1998;63:371-80 pubmed
  11. Wimmer J, Fujinaga K, Taube R, Cujec T, Zhu Y, Peng J, et al. Interactions between Tat and TAR and human immunodeficiency virus replication are facilitated by human cyclin T1 but not cyclins T2a or T2b. Virology. 1999;255:182-9 pubmed
    ..By combining individually with CDK9, cyclin T1 or related cyclins T2a and T2b form distinct positive transcription elongation factor b (P-TEFb) ..
  12. Nguyen V, Kiss T, Michels A, Bensaude O. 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes. Nature. 2001;414:322-5 pubmed
    ..CTD) of the largest polymerase subunit by a transcription elongation factor, P-TEFb, which comprises the kinase CDK9 and cyclin T1 or T2 (ref. 1)...
  13. Durand L, Roizman B. Role of cdk9 in the optimization of expression of the genes regulated by ICP22 of herpes simplex virus 1. J Virol. 2008;82:10591-9 pubmed publisher
    ..ICP22 binds the cyclin-dependent kinase 9 (cdk9) but not cdk7, and this complex in conjunction with viral protein kinases phosphorylates the carboxyl terminus of ..
  14. Byers S, Price J, Cooper J, Li Q, Price D. HEXIM2, a HEXIM1-related protein, regulates positive transcription elongation factor b through association with 7SK. J Biol Chem. 2005;280:16360-7 pubmed
    ..Our results provide strong evidence that HEXIM2 is a regulator of P-TEFb function. Furthermore, our results support the idea that the utilization of HEXIM1 or HEXIM2 to bind and inhibit P-TEFb can be differentially regulated in vivo. ..
  15. Ivanov D, Kwak Y, Nee E, Guo J, García Martínez L, Gaynor R. Cyclin T1 domains involved in complex formation with Tat and TAR RNA are critical for tat-activation. J Mol Biol. 1999;288:41-56 pubmed
    ..Recently, it has been demonstrated that the cellular kinase CDK9 and its binding partner cyclin T1 are involved in regulating transcriptional elongation and tat-activation...
  16. Peng J, Zhu Y, Milton J, Price D. Identification of multiple cyclin subunits of human P-TEFb. Genes Dev. 1998;12:755-62 pubmed
    ..Drosophila P-TEFb was identified recently as a cyclin-dependent kinase (CDK9) paired with a cyclin subunit (cyclin T)...
  17. Giacinti C, Bagella L, Puri P, Giordano A, Simone C. MyoD recruits the cdk9/cyclin T2 complex on myogenic-genes regulatory regions. J Cell Physiol. 2006;206:807-13 pubmed
    ..We show that MyoD recruits cdk9/cyclin T2, together with the histone acetyltransferases p300 and PCAF, and the chromatin remodeling complex SWI/SNF,..
  18. Simone C, Stiegler P, Bagella L, Pucci B, Bellan C, De Falco G, et al. Activation of MyoD-dependent transcription by cdk9/cyclin T2. Oncogene. 2002;21:4137-48 pubmed
    ..Unlike the other cdks, cdk9 is not serum- or cell cycle-regulated and is instead involved in the regulation of transcriptional elongation by ..
  19. Kanazawa S, Soucek L, Evan G, Okamoto T, Peterlin B. c-Myc recruits P-TEFb for transcription, cellular proliferation and apoptosis. Oncogene. 2003;22:5707-11 pubmed
    ..The cyclin-dependent kinase 9 (Cdk9) in P-TEFb then phosporylates the C-terminal domain of RNA polymerase II, which is required for the transition from ..
  20. Lu H, Li Z, Xue Y, Schulze Gahmen U, Johnson J, Krogan N, et al. AFF1 is a ubiquitous P-TEFb partner to enable Tat extraction of P-TEFb from 7SK snRNP and formation of SECs for HIV transactivation. Proc Natl Acad Sci U S A. 2014;111:E15-24 pubmed publisher
    ..complexes have been thought to share no components other than the core P-TEFb subunits cyclin-dependent kinase 9 (CDK9) and cyclin T (CycT, T1, T2a, and T2b)...
  21. Czudnochowski N, Bösken C, Geyer M. Serine-7 but not serine-5 phosphorylation primes RNA polymerase II CTD for P-TEFb recognition. Nat Commun. 2012;3:842 pubmed publisher
    ..Inhibition of P-TEFb activity is mediated by two regions in Hexim1 that act synergistically on Cdk9 and Cyclin T1...
  22. Zhu Y, PE ERY T, Peng J, Ramanathan Y, Marshall N, Marshall T, et al. Transcription elongation factor P-TEFb is required for HIV-1 tat transactivation in vitro. Genes Dev. 1997;11:2622-32 pubmed
    ..Sequence comparison suggests that a protein with 72% identity, PITALRE, could be the human homolog of the Drosophila protein...
  23. Gold M, Yang X, Herrmann C, Rice A. PITALRE, the catalytic subunit of TAK, is required for human immunodeficiency virus Tat transactivation in vivo. J Virol. 1998;72:4448-53 pubmed
    The human cdc2-related kinase PITALRE is the catalytic component of TAK, the Tat-associated kinase. Previously, we have proposed that TAK is a cellular factor that mediates Tat transactivation function...
  24. Pirngruber J, Shchebet A, Schreiber L, Shema E, Minsky N, Chapman R, et al. CDK9 directs H2B monoubiquitination and controls replication-dependent histone mRNA 3'-end processing. EMBO Rep. 2009;10:894-900 pubmed publisher
    ..Cyclin-dependent kinase 9 (CDK9) regulates gene expression by phosphorylating transcriptional regulatory proteins, including the RNA polymerase II ..
  25. Kanazawa S, Okamoto T, Peterlin B. Tat competes with CIITA for the binding to P-TEFb and blocks the expression of MHC class II genes in HIV infection. Immunity. 2000;12:61-70 pubmed
    ..By binding to the same surface in the cyclin T1, which together with CDK9 forms the positive transcription elongation factor b (P-TEFb) complex, Tat inhibits CIITA...
  26. Bannwarth S, Gatignol A. HIV-1 TAR RNA: the target of molecular interactions between the virus and its host. Curr HIV Res. 2005;3:61-71 pubmed
    ..The Tat-Cyclin T1-CDK9 complex is the main component in the trans-activation of HIV-1 and its affinity for TAR is regulated through Tat ..
  27. Stevens M, De Clercq E, Balzarini J. The regulation of HIV-1 transcription: molecular targets for chemotherapeutic intervention. Med Res Rev. 2006;26:595-625 pubmed
    ..The complex of Tat with p-TEFb then binds the loop structures of TAR RNA thereby positioning CDK9 to phosphorylate the cellular RNA polymerase II...
  28. Ghose R, Liou L, Herrmann C, Rice A. Induction of TAK (cyclin T1/P-TEFb) in purified resting CD4(+) T lymphocytes by combination of cytokines. J Virol. 2001;75:11336-43 pubmed
    ..Tat function is mediated by a cellular protein kinase known as TAK (cyclin T1/P-TEFb) that is composed of Cdk9 and cyclin T1...
  29. Nekhai S, Jeang K. Transcriptional and post-transcriptional regulation of HIV-1 gene expression: role of cellular factors for Tat and Rev. Future Microbiol. 2006;1:417-26 pubmed
    ..Tat interacts with protein kinase complexes Cdk9/cyclin T1 and Cdk2/cyclin E; acetyltransferases p300/CBP, p300/CBP-associated factor and hGCN5; protein ..
  30. Estable M, Naghavi M, Kato H, Xiao H, Qin J, Vahlne A, et al. 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;9:234-45 pubmed
    Positive transcription elongation factor-b (P-TEFb) contains CDK9 and cyclin T(1)...
  31. Zhou M, Nekhai S, Bharucha D, Kumar A, Ge H, Price D, et al. TFIIH inhibits CDK9 phosphorylation during human immunodeficiency virus type 1 transcription. J Biol Chem. 2001;276:44633-40 pubmed
    ..HIV-1), transcription elongation by recruitment of the human transcription elongation factor P-TEFb, consisting of CDK9 and cyclin T1, to the TAR RNA structure...
  32. Mahmoudi T, Parra M, Vries R, Kauder S, Verrijzer C, Ott M, et al. The SWI/SNF chromatin-remodeling complex is a cofactor for Tat transactivation of the HIV promoter. J Biol Chem. 2006;281:19960-8 pubmed
    ..This synergism depended on the acetyltransferase activity of p300 and on Tat Lys(50) and Lys(51). In conclusion, Tat-mediated activation of the HIV promoter requires the SWI/SNF complex in synergy with the coactivator p300. ..
  33. Michels A, Bensaude O. RNA-driven cyclin-dependent kinase regulation: when CDK9/cyclin T subunits of P-TEFb meet their ribonucleoprotein partners. Biotechnol J. 2008;3:1022-32 pubmed publisher
    The positive transcription elongation factor (P-TEFb) consists of CDK9, a cyclin-dependent kinase and its cyclin T partner. It is required for transcription of most class II genes. Its activity is regulated by non-coding RNAs...
  34. Kwak Y, Ivanov D, Guo J, Nee E, Gaynor R. Role of the human and murine cyclin T proteins in regulating HIV-1 tat-activation. J Mol Biol. 1999;288:57-69 pubmed
    ..The data indicate that a specific residue in the cyclin T proteins is required for their in vitro interaction with Tat and their ability to stimulate in vivo tat-activation. ..
  35. Ivanov D, Kwak Y, Guo J, Gaynor R. Domains in the SPT5 protein that modulate its transcriptional regulatory properties. Mol Cell Biol. 2000;20:2970-83 pubmed
    ..Recent data suggest that P-TEFb, which is composed of CDK9 and cyclin T1, is also critical in regulating transcriptional elongation by SPT4 and SPT5...
  36. Marcello A, Zoppe M, Giacca M. Multiple modes of transcriptional regulation by the HIV-1 Tat transactivator. IUBMB Life. 2001;51:175-81 pubmed
    ..of transcriptional elongation is the consequence of the interaction of Tat with cyclin T1, the cyclin component of CDK9, which phosphorylates the carboxy-terminal domain of RNA polymerase II to enhance its processivity...
  37. Barboric M, Zhang F, Besenicar M, Plemenitas A, Peterlin B. Ubiquitylation of Cdk9 by Skp2 facilitates optimal Tat transactivation. J Virol. 2005;79:11135-41 pubmed
    ..We found that cyclin-dependent kinase 9 (Cdk9), the catalytic subunit of P-TEFb, is ubiquitylated in vivo...
  38. Garriga J, Mayol X, Grana X. The CDC2-related kinase PITALRE is the catalytic subunit of active multimeric protein complexes. Biochem J. 1996;319 ( Pt 1):293-8 pubmed
    b>PITALRE is a human protein kinase identified by means of its partial sequence identity to the cell division cycle regulatory kinase CDC2...
  39. Wei P, Garber M, Fang S, Fischer W, Jones K. 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;92:451-62 pubmed
    ..Cyclin T is a partner for CDK9, an RNAPII transcription elongation factor...
  40. Kim J, Sharp P. 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;276:12317-23 pubmed
    The CDK9-cyclin T kinase complex, positive transcription elongation factor b (P-TEFb), stimulates the process of elongation of RNA polymerase (Pol) II during transcription of human immunodeficiency virus...
  41. Chiu Y, Cao H, Jacque J, Stevenson M, Rana T. Inhibition of human immunodeficiency virus type 1 replication by RNA interference directed against human transcription elongation factor P-TEFb (CDK9/CyclinT1). J Virol. 2004;78:2517-29 pubmed
    The human positive transcription elongation factor P-TEFb is composed of two subunits, cyclin T1 (hCycT1) and CDK9, and is involved in transcriptional regulation of cellular genes as well as human immunodeficiency virus type 1 (HIV-1) ..
  42. Luo Z, Lin C, Shilatifard A. The super elongation complex (SEC) family in transcriptional control. Nat Rev Mol Cell Biol. 2012;13:543-7 pubmed publisher
    ..Recent studies have shown that the SEC belongs to a larger family of SEC-like complexes, which includes SEC-L2 and SEC-L3, each with distinct gene target specificities. ..
  43. Dong C, Kwas C, Wu L. Transcriptional restriction of human immunodeficiency virus type 1 gene expression in undifferentiated primary monocytes. J Virol. 2009;83:3518-27 pubmed publisher
    ..Two critical cellular cofactors of HIV-1 Tat, cyclin T1 (CycT1) and cyclin-dependent kinase 9 (CDK9), are required for LTR-directed HIV-1 transcription...
  44. 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;17:7395-403 pubmed
    ..b>PITALRE, a member of the Cdc2 family of protein kinases, is the catalytic subunit of P-TEFb...
  45. Yik J, Chen R, Nishimura R, Jennings J, Link A, Zhou Q. Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA. Mol Cell. 2003;12:971-82 pubmed
    The positive transcriptional elongation factor b (P-TEFb), consisting of CDK9 and cyclin T, stimulates transcription by phosphorylating RNA polymerase II. It becomes inactivated when associated with the abundant 7SK snRNA...
  46. Yang Z, Yik J, Chen R, He N, Jang M, Ozato K, et al. Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4. Mol Cell. 2005;19:535-45 pubmed
    The cyclinT1/Cdk9 heterodimer that constitutes core P-TEFb is generally presumed to be the transcriptionally active form for stimulating RNA polymerase II elongation...
  47. Treand C, du Chéné I, Brès V, Kiernan R, Benarous R, Benkirane M, et al. Requirement for SWI/SNF chromatin-remodeling complex in Tat-mediated activation of the HIV-1 promoter. EMBO J. 2006;25:1690-9 pubmed
    ..These data show the requirement of Tat-mediated recruitment of SWI/SNF chromatin-remodeling complex to HIV-1 promoter in the activation of the LTR. ..
  48. Williams S, Kwon H, Chen L, Greene W. Sustained induction of NF-kappa B is required for efficient expression of latent human immunodeficiency virus type 1. J Virol. 2007;81:6043-56 pubmed
    ..Cyclin-dependent kinase 9 (CDK9) and serine-2-phosphorylated RNA Pol II were rapidly recruited to the HIV-1 LTR after NF-kappaB induction; however, ..
  49. D ORSO I, Frankel A. RNA-mediated displacement of an inhibitory snRNP complex activates transcription elongation. Nat Struct Mol Biol. 2010;17:815-21 pubmed publisher
    ..Recruitment of an inhibitory snRNP complex at an early stage in the transcription cycle provides a new paradigm for controlling gene expression with a noncoding RNA. ..
  50. Yang X, Gold M, Tang D, Lewis D, Aguilar Cordova E, Rice A, et al. TAK, an HIV Tat-associated kinase, is a member of the cyclin-dependent family of protein kinases and is induced by activation of peripheral blood lymphocytes and differentiation of promonocytic cell lines. Proc Natl Acad Sci U S A. 1997;94:12331-6 pubmed
    ..Virol. 69, 1612-1620]. We show here that the catalytic subunit of TAK is a known human kinase previously named PITALRE, which is a member of the cyclin-dependent family of proteins...
  51. Flores O, Lee G, Kessler J, Miller M, Schlief W, Tomassini J, et al. Host-cell positive transcription elongation factor b kinase activity is essential and limiting for HIV type 1 replication. Proc Natl Acad Sci U S A. 1999;96:7208-13 pubmed
    ..Selective inhibition of the P-TEFb kinase may therefore provide a novel approach for developing chemotherapeutic agents against HIV-1. ..
  52. Chen R, Yang Z, Zhou Q. Phosphorylated positive transcription elongation factor b (P-TEFb) is tagged for inhibition through association with 7SK snRNA. J Biol Chem. 2004;279:4153-60 pubmed
    The positive transcription elongation factor b (P-TEFb), comprising CDK9 and cyclin T, stimulates transcription of cellular and viral genes by phosphorylating RNA polymerase II...
  53. Gordon V, Bhadel S, Wunderlich W, Zhang J, Ficarro S, Mollah S, et al. CDK9 regulates AR promoter selectivity and cell growth through serine 81 phosphorylation. Mol Endocrinol. 2010;24:2267-80 pubmed publisher
    ..We observed cyclin-dependent kinase (CDK)9 association with the AR. CDK9 phosphorylates the AR on S81 in vitro...
  54. Benedikt A, Baltruschat S, Scholz B, Bursen A, Arrey T, Meyer B, et al. The leukemogenic AF4-MLL fusion protein causes P-TEFb kinase activation and altered epigenetic signatures. Leukemia. 2011;25:135-44 pubmed publisher
    ..Thus, we propose that these two processes are key to trigger cellular reprogramming that leads to the onset of acute leukemia. ..
  55. Liu M, Hsu J, Chan C, Li Z, Zhou Q. The ubiquitin ligase Siah1 controls ELL2 stability and formation of super elongation complexes to modulate gene transcription. Mol Cell. 2012;46:325-34 pubmed publisher
    ..Given its importance in formation of SECs, the Siah1 ubiquitination pathway provides a fresh avenue for developing strategies to control disease-related transcription. ..
  56. Garber M, Wei P, Kewalramani V, Mayall T, Herrmann C, Rice A, et al. The interaction between HIV-1 Tat and human cyclin T1 requires zinc and a critical cysteine residue that is not conserved in the murine CycT1 protein. Genes Dev. 1998;12:3512-27 pubmed
    ..at the carboxy-terminal edge of the cyclin domain, and we show that hCycT1 can interact simultaneously with Tat and CDK9 on TAR RNA in vitro...
  57. Larochelle S, Batliner J, Gamble M, Barboza N, Kraybill B, Blethrow J, et al. Dichotomous but stringent substrate selection by the dual-function Cdk7 complex revealed by chemical genetics. Nat Struct Mol Biol. 2006;13:55-62 pubmed
    ..Thus, Cdk7 accomplishes dual functions in cell-cycle control and transcription not through promiscuity but through distinct, stringent modes of substrate recognition. ..
  58. Bisgrove D, Mahmoudi T, Henklein P, Verdin E. Conserved P-TEFb-interacting domain of BRD4 inhibits HIV transcription. Proc Natl Acad Sci U S A. 2007;104:13690-5 pubmed
    ..Incubation of cells with a synthetic peptide containing the C-terminal domain of BRD4 interferes with transactivation of the HIV promoter by the Tat protein. ..
  59. Sunagawa Y, Morimoto T, Takaya T, Kaichi S, Wada H, Kawamura T, et al. Cyclin-dependent kinase-9 is a component of the p300/GATA4 complex required for phenylephrine-induced hypertrophy in cardiomyocytes. J Biol Chem. 2010;285:9556-68 pubmed publisher
    ..By tandem affinity purification and mass spectrometric analyses, we identified cyclin-dependent kinase-9 (Cdk9) as a novel GATA4-binding partner. Cdk9 also formed a complex with p300 as well as GATA4 and cyclin T1...
  60. Ramakrishnan R, Rice A. Cdk9 T-loop phosphorylation is regulated by the calcium signaling pathway. J Cell Physiol. 2012;227:609-17 pubmed publisher
    ..The core P-TEFb complex is composed of Cdk9 and Cyclin T and is essential for the expression of most protein coding genes...
  61. Fong Y, Zhou Q. Stimulatory effect of splicing factors on transcriptional elongation. Nature. 2001;414:929-33 pubmed
    ..Because the TAT-SF1-U snRNP complex also stimulates splicing in vitro, it may serve as a dual-function factor to couple transcription and splicing and to facilitate their reciprocal activation. ..
  62. Wang Y, Dow E, Liang Y, Ramakrishnan R, Liu H, Sung T, et al. Phosphatase PPM1A regulates phosphorylation of Thr-186 in the Cdk9 T-loop. J Biol Chem. 2008;283:33578-84 pubmed publisher
    b>Cdk9 is the catalytic subunit of a general RNA polymerase II elongation factor known as positive transcription elongation factor b (P-TEFb)...
  63. Siliciano R, Greene W. HIV latency. Cold Spring Harb Perspect Med. 2011;1:a007096 pubmed publisher
    ..Several approaches are under exploration for reactivating latent virus with the hope that this will allow elimination of the latent reservoir. ..
  64. De Falco G, Bagella L, Claudio P, De Luca A, Fu Y, Calabretta B, et al. Physical interaction between CDK9 and B-Myb results in suppression of B-Myb gene autoregulation. Oncogene. 2000;19:373-9 pubmed
    ..We report in this study that CDK9, the cyclin T associated kinase, which phosphorylates and activates RNA-Polymerase II, suppresses B-Myb ..
  65. Liu H, Rice A. Genomic organization and characterization of promoter function of the human CDK9 gene. Gene. 2000;252:51-9 pubmed
    b>CDK9 is the catalytic subunit of a general RNA polymerase II (RNAP II) elongation factor termed p-TEFb which is targeted by the human immunodeficiency virus (HIV) Tat protein to activate elongation of the integrated proviral genome...
  66. Garriga J, Bhattacharya S, Calbo J, Marshall R, Truongcao M, Haines D, et al. CDK9 is constitutively expressed throughout the cell cycle, and its steady-state expression is independent of SKP2. Mol Cell Biol. 2003;23:5165-73 pubmed
    b>CDK9 is a CDC2-related kinase and the catalytic subunit of the positive-transcription elongation factor b and the Tat-activating kinase...
  67. Yang Z, He N, Zhou Q. Brd4 recruits P-TEFb to chromosomes at late mitosis to promote G1 gene expression and cell cycle progression. Mol Cell Biol. 2008;28:967-76 pubmed
    ..It also functions as an associated factor and positive regulator of P-TEFb, a Cdk9-cyclin T1 heterodimer that stimulates transcriptional elongation by phosphorylating RNA polymerase II...
  68. Ramakrishnan R, Dow E, Rice A. Characterization of Cdk9 T-loop phosphorylation in resting and activated CD4(+) T lymphocytes. J Leukoc Biol. 2009;86:1345-50 pubmed publisher
    The cellular kinase complex P-TEFb is composed of Cdk9 and cyclin T, and it is required for expression of most protein-coding genes by RNAP II...
  69. Fujinaga K, Taube R, Wimmer J, Cujec T, Peterlin B. Interactions between human cyclin T, Tat, and the transactivation response element (TAR) are disrupted by a cysteine to tyrosine substitution found in mouse cyclin T. Proc Natl Acad Sci U S A. 1999;96:1285-90 pubmed
    ..These findings reveal the molecular basis for the restriction of Tat transactivation in rodent cells. ..
  70. Yik J, Chen R, Pezda A, Samford C, Zhou Q. A human immunodeficiency virus type 1 Tat-like arginine-rich RNA-binding domain is essential for HEXIM1 to inhibit RNA polymerase II transcription through 7SK snRNA-mediated inactivation of P-TEFb. Mol Cell Biol. 2004;24:5094-105 pubmed
    The HEXIM1 protein inhibits the kinase activity of P-TEFb (CDK9/cyclin T) to suppress RNA polymerase II transcriptional elongation in a process that specifically requires the 7SK snRNA, which mediates the interaction of HEXIM1 with P-TEFb...
  71. Garber M, Mayall T, Suess E, Meisenhelder J, Thompson N, Jones K. CDK9 autophosphorylation regulates high-affinity binding of the human immunodeficiency virus type 1 tat-P-TEFb complex to TAR RNA. Mol Cell Biol. 2000;20:6958-69 pubmed
    Human immunodeficiency virus type 1 (HIV-1) Tat interacts with cyclin T1 (CycT1), a regulatory partner of CDK9 in the positive transcription elongation factor (P-TEFb) complex, and binds cooperatively with CycT1 to TAR RNA to recruit P-..
  72. Lee D, Duan H, Chang C. Androgen receptor interacts with the positive elongation factor P-TEFb and enhances the efficiency of transcriptional elongation. J Biol Chem. 2001;276:9978-84 pubmed
    ..effort to further dissect the mechanisms implicated in AR transactivation, we report here that AR interacts with PITALRE, a kinase subunit of positive elongation factor b (P-TEFb)...
  73. 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. In this study, we systematically compared the phosphorylation of different recombinant CTD substrates by ..
  74. Mancebo H, Lee G, Flygare J, Tomassini J, Luu P, Zhu Y, et al. P-TEFb kinase is required for HIV Tat transcriptional activation in vivo and in vitro. Genes Dev. 1997;11:2633-44 pubmed
    ..Loss of Tat transactivation in extracts depleted of the kinase subunit of human P-TEFb, PITALRE, was reversed by addition of partially purified human P-TEFb...
  75. Herrmann C, Mancini M. The Cdk9 and cyclin T subunits of TAK/P-TEFb localize to splicing factor-rich nuclear speckle regions. J Cell Sci. 2001;114:1491-503 pubmed
    ..TAK/P-TEFb is composed of Cdk9 and cyclin T and serves as the cellular cofactor for the human immunodeficiency virus transactivator Tat protein...
  76. Bourgeois C, Kim Y, Churcher M, West M, Karn J. Spt5 cooperates with human immunodeficiency virus type 1 Tat by preventing premature RNA release at terminator sequences. Mol Cell Biol. 2002;22:1079-93 pubmed
    ..transcription elongation by stimulating the Tat-activated kinase (TAK/p-TEFb), a protein kinase composed of CDK9 and its cyclin partner, cyclin T1...
  77. Hoque M, Young T, Lee C, Serrero G, Mathews M, PE ERY T. The growth factor granulin interacts with cyclin T1 and modulates P-TEFb-dependent transcription. Mol Cell Biol. 2003;23:1688-702 pubmed
    Cyclin T1, together with the kinase CDK9, is a component of the transcription elongation factor P-TEFb which binds the human immunodeficiency virus type 1 (HIV-1) transactivator Tat...
  78. Hou T, Ray S, Brasier A. The functional role of an interleukin 6-inducible CDK9.STAT3 complex in human gamma-fibrinogen gene expression. J Biol Chem. 2007;282:37091-102 pubmed
    ..of the APR, we investigated the requirement of an IL-6-inducible complex of STAT3 with cyclin-dependent kinase 9 (CDK9) on gamma-FBG expression in HepG2 hepatocarcinoma cells...
  79. Krueger B, Varzavand K, Cooper J, Price D. The mechanism of release of P-TEFb and HEXIM1 from the 7SK snRNP by viral and cellular activators includes a conformational change in 7SK. PLoS ONE. 2010;5:e12335 pubmed publisher
    ..Based on our findings, we hypothesize that reincorporation of HEXIM1 into the 7SK snRNP is likely the regulated step of reassembly of the 7SK snRNP containing P-TEFb. ..
  80. Muniz L, Egloff S, Ughy B, Jady B, Kiss T. Controlling cellular P-TEFb activity by the HIV-1 transcriptional transactivator Tat. PLoS Pathog. 2010;6:e1001152 pubmed publisher
  81. Devaiah B, Singer D. Cross-talk among RNA polymerase II kinases modulates C-terminal domain phosphorylation. J Biol Chem. 2012;287:38755-66 pubmed publisher
    ..We report that three CTD kinases, CDK7, CDK9, and BRD4, engage in cross-talk, modulating their subsequent CTD phosphorylation...
  82. Larochelle S, Amat R, Glover Cutter K, Sansó M, Zhang C, Allen J, et al. Cyclin-dependent kinase control of the initiation-to-elongation switch of RNA polymerase II. Nat Struct Mol Biol. 2012;19:1108-15 pubmed publisher
    ..Pause release depends on Cdk9-cyclin T1 (P-TEFb); Cdk7 is also required for Cdk9-activating phosphorylation and Cdk9-dependent downstream events--..
  83. Zhou Q, Chen D, Pierstorff E, Luo K. Transcription elongation factor P-TEFb mediates Tat activation of HIV-1 transcription at multiple stages. EMBO J. 1998;17:3681-91 pubmed
    ..Recently, a human transcription elongation factor P-TEFb, consisting of CDK9 kinase, cyclin T and other associated factors, has been shown to interact with Tat to restore Tat activation in ..
  84. Fu T, Peng J, Lee G, Price D, Flores O. Cyclin K functions as a CDK9 regulatory subunit and participates in RNA polymerase II transcription. J Biol Chem. 1999;274:34527-30 pubmed
    ..The P-TEFb complex isolated from mammalian cells contains a catalytic subunit (CDK9), a cyclin subunit (cyclin T1 or cyclin T2), and additional, yet unidentified, polypeptides of unknown function...
  85. Fong Y, Zhou Q. Relief of two built-In autoinhibitory mechanisms in P-TEFb is required for assembly of a multicomponent transcription elongation complex at the human immunodeficiency virus type 1 promoter. Mol Cell Biol. 2000;20:5897-907 pubmed
    ..We show here that the P-TEFb heterodimer of Cdk9-cyclin T1 is intrinsically incapable of forming a stable complex with Tat and TAR due to two built-in ..
  86. Ping Y, Rana T. 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;276:12951-8 pubmed
    ..These findings reveal a molecular mechanism for the negative and positive regulation of transcriptional elongation at the HIV-1 promoter. ..
  87. 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...
  88. Barboric M, Nissen R, Kanazawa S, Jabrane Ferrat N, Peterlin B. NF-kappaB binds P-TEFb to stimulate transcriptional elongation by RNA polymerase II. Mol Cell. 2001;8:327-37 pubmed
    ..Remarkably, DRB inhibition sensitized cells to TNF-alpha-induced apoptosis. Thus, NF-kappaB requires P-TEFb to stimulate the elongation of transcription and P-TEFb plays an unexpected role in regulating apoptosis. ..
  89. Kiernan R, Emiliani S, Nakayama K, Castro A, Labbe J, Lorca T, et al. Interaction between cyclin T1 and SCF(SKP2) targets CDK9 for ubiquitination and degradation by the proteasome. Mol Cell Biol. 2001;21:7956-70 pubmed
    b>CDK9 paired with cyclin T1 forms the human P-TEFb complex and stimulates productive transcription through phosphorylation of the RNA polymerase II C-terminal domain...
  90. Fujinaga K, Irwin D, Geyer M, Peterlin B. Optimized chimeras between kinase-inactive mutant Cdk9 and truncated cyclin T1 proteins efficiently inhibit Tat transactivation and human immunodeficiency virus gene expression. J Virol. 2002;76:10873-81 pubmed
    ..and thus HIV replication, we constructed mutant hCycT1 proteins that are defective in binding its kinase partner, Cdk9, or TAR...
  91. Liu H, Herrmann C. Differential localization and expression of the Cdk9 42k and 55k isoforms. J Cell Physiol. 2005;203:251-60 pubmed
    ..There are two known isoforms of Cdk9: a 42 kDa protein (42k, originally identified as PITALRE) and a more recently identified 55 kDa form (55k)...
  92. Fu J, Yoon H, Qin J, Wong J. Regulation of P-TEFb elongation complex activity by CDK9 acetylation. Mol Cell Biol. 2007;27:4641-51 pubmed
    P-TEFb, comprised of CDK9 and a cyclin T subunit, is a global transcriptional elongation factor important for most RNA polymerase II (pol II) transcription...