CCNT1

Summary

Gene Symbol: CCNT1
Description: cyclin T1
Alias: CCNT, CYCT1, HIVE1, cyclin-T1, CDK9-associated C-type protein, MLLT10/CCNT1 fusion, cyclin C-related protein, human immunodeficiency virus type 1 (HIV-1) expression (elevated) 1
Species: human
Products:     CCNT1

Top Publications

  1. 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
    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...
  2. Eberhardy S, Farnham P. Myc recruits P-TEFb to mediate the final step in the transcriptional activation of the cad promoter. J Biol Chem. 2002;277:40156-62 pubmed
    ..We have found that cyclin T1 binding to Myc localizes to the highly conserved Myc Box I, whereas cdk8 binding localizes to the amino-terminal ..
  3. Napolitano G, Mazzocco A, Fraldi A, Majello B, Lania L. Functional inactivation of Cdk9 through oligomerization chain reaction. Oncogene. 2003;22:4882-8 pubmed
    ..Here, we present the successful application of the OCR strategy for inactivation of the heterodimeric Cdk9/cyclin T1 complex...
  4. Michels A, Fraldi A, Li Q, Adamson T, Bonnet F, Nguyen V, et al. Binding of the 7SK snRNA turns the HEXIM1 protein into a P-TEFb (CDK9/cyclin T) inhibitor. EMBO J. 2004;23:2608-19 pubmed
    ..We propose that the RNA-binding domain of HEXIM1 mediates its association with 7SK and that P-TEFb then enters the complex through association with HEXIM1. ..
  5. Barboric M, Peterlin B. A new paradigm in eukaryotic biology: HIV Tat and the control of transcriptional elongation. PLoS Biol. 2005;3:e76 pubmed
  6. Cho S, Schroeder S, Kaehlcke K, Kwon H, Pedal A, Herker E, et al. Acetylation of cyclin T1 regulates the equilibrium between active and inactive P-TEFb in cells. EMBO J. 2009;28:1407-17 pubmed publisher
    ..P-TEFb exists in two forms in cells, an active form composed of cyclin T1 and CDK9 and an inactive form, in which cyclin T1/CDK9 is sequestered by Hexim1 and 7SK snRNA...
  7. Budhiraja S, Famiglietti M, Bosque A, Planelles V, Rice A. Cyclin T1 and CDK9 T-loop phosphorylation are downregulated during establishment of HIV-1 latency in primary resting memory CD4+ T cells. J Virol. 2013;87:1211-20 pubmed publisher
    P-TEFb, a cellular kinase composed of Cyclin T1 and CDK9, is essential for processive HIV-1 transcription. P-TEFb activity is dependent on phosphorylation of Thr186 in the CDK9 T loop...
  8. Sobhian B, Laguette N, Yatim A, Nakamura M, Levy Y, Kiernan R, et al. HIV-1 Tat assembles a multifunctional transcription elongation complex and stably associates with the 7SK snRNP. Mol Cell. 2010;38:439-51 pubmed publisher
    ..MLL-fusion partners and PAF1 are required for Tat transactivation. Tatcom2 is composed of CDK9, CycT1, and 7SK snRNP lacking HEXIM...
  9. 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 ..

More Information

Publications118 found, 100 shown here

  1. Brès V, Yoshida T, Pickle L, Jones K. SKIP interacts with c-Myc and Menin to promote HIV-1 Tat transactivation. Mol Cell. 2009;36:75-87 pubmed publisher
    ..Thus, SKIP acts with c-Myc and Menin to promote HIV-1 Tat:P-TEFb transcription at an elongation step that is bypassed under stress. ..
  2. Czudnochowski N, Vollmuth F, Baumann S, Vogel Bachmayr K, Geyer M. Specificity of Hexim1 and Hexim2 complex formation with cyclin T1/T2, importin alpha and 7SK snRNA. J Mol Biol. 2010;395:28-41 pubmed publisher
    ..Using isothermal titration calorimetry, we observed higher affinities for Cyclin T1-Hexim1 and Cyclin T2-Hexim2 complex formations compared with the interactions in reverse...
  3. 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. ..
  4. Garriga J, Peng J, Parreño M, Price D, Henderson E, Grana X. Upregulation of cyclin T1/CDK9 complexes during T cell activation. Oncogene. 1998;17:3093-102 pubmed
    b>Cyclin T1 has been identified recently as a regulatory subunit of CDK9 and as a component of the transcription elongation factor P-TEFb...
  5. 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. ..
  6. Yu W, Ramakrishnan R, Wang Y, Chiang K, Sung T, Rice A. Cyclin T1-dependent genes in activated CD4 T and macrophage cell lines appear enriched in HIV-1 co-factors. PLoS ONE. 2008;3:e3146 pubmed publisher
    ..One critical co-factor is Cyclin T1, a subunit of a general RNA polymerase II elongation factor known as P-TEFb...
  7. Kiernan R, Vanhulle C, Schiltz L, Adam E, Xiao H, Maudoux F, et al. HIV-1 tat transcriptional activity is regulated by acetylation. EMBO J. 1999;18:6106-18 pubmed
    ..These data suggest that acetylation of Tat regulates two discrete and functionally critical steps in transcription, binding to an RNAP II CTD-kinase and release of Tat from TAR RNA. ..
  8. 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
    ..the largest polymerase subunit by a transcription elongation factor, P-TEFb, which comprises the kinase CDK9 and cyclin T1 or T2 (ref. 1)...
  9. 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. ..
  10. 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
  11. Karn J, Stoltzfus C. Transcriptional and posttranscriptional regulation of HIV-1 gene expression. Cold Spring Harb Perspect Med. 2012;2:a006916 pubmed publisher
    ..In cells that are not fully activated, limiting levels of Tat and Rev act as potent blocks to premature virus production. ..
  12. Herrmann C, Rice A. Lentivirus Tat proteins specifically associate with a cellular protein kinase, TAK, that hyperphosphorylates the carboxyl-terminal domain of the large subunit of RNA polymerase II: candidate for a Tat cofactor. J Virol. 1995;69:1612-20 pubmed
    ..Taken together, these results imply that TAK is a very promising candidate for a cellular factor that mediates Tat transactivation. ..
  13. 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
    The human cyclin T1 (hCycT1) protein from the positive transcription elongation factor b (P-TEFb) binds the transactivator Tat and the transactivation response (TAR) RNA stem loop from human immunodeficiency virus type 1 (HIV)...
  14. 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 autoinhibitory ..
  15. Yu W, Wang Y, Shaw C, Qin X, Rice A. Induction of the HIV-1 Tat co-factor cyclin T1 during monocyte differentiation is required for the regulated expression of a large portion of cellular mRNAs. Retrovirology. 2006;3:32 pubmed
    ..polymerase II elongation factor, is composed of CDK9 (cyclin-dependent kinase 9) as a catalytic unit and either cyclin T1, T2 or K as a regulatory subunit. The cyclin T1/P-TEFb complex is targeted by HIV to mediate Tat transactivation...
  16. Bieniasz P, Grdina T, Bogerd H, Cullen B. Recruitment of cyclin T1/P-TEFb to an HIV type 1 long terminal repeat promoter proximal RNA target is both necessary and sufficient for full activation of transcription. Proc Natl Acad Sci U S A. 1999;96:7791-6 pubmed
    ..element encoded within the LTR and is known to require the recruitment of a complex consisting of Tat and the cyclin T1 (CycT1) component of positive transcription elongation factor b (P-TEFb) to TAR...
  17. Fraldi A, Licciardo P, Majello B, Giordano A, Lania L. Distinct regions of cyclinT1 are required for binding to CDK9 and for recruitment to the HIV-1 Tat/TAR complex. J Cell Biochem Suppl. 2001;Suppl 36:247-53 pubmed
    ..with the cyclinT1, the regulatory partner of CDK9, results in a specific recruitment of the heterodimer CycT1/CDK9 complex to TAR, whereby it promotes transcription elongation of the HIV-1 LTR-mediated transcription...
  18. He N, Pezda A, Zhou Q. Modulation of a P-TEFb functional equilibrium for the global control of cell growth and differentiation. Mol Cell Biol. 2006;26:7068-76 pubmed
    ..Concurrently, the P-TEFb equilibrium was shifted overwhelmingly toward the 7SK snRNP side. Together, these data link the P-TEFb equilibrium to the intracellular transcriptional demand and proliferative/differentiated states of cells. ..
  19. Yedavalli V, Benkirane M, Jeang K. Tat and trans-activation-responsive (TAR) RNA-independent induction of HIV-1 long terminal repeat by human and murine cyclin T1 requires Sp1. J Biol Chem. 2003;278:6404-10 pubmed
    P-TEFb, cyclin T1 + CDK9, is needed for the expression of cellular promoters and primate lentiviral long terminal repeats (LTRs)...
  20. Agbottah E, Deng L, Dannenberg L, Pumfery A, Kashanchi F. Effect of SWI/SNF chromatin remodeling complex on HIV-1 Tat activated transcription. Retrovirology. 2006;3:48 pubmed
    ..We propose a model where unmodified Tat is involved in binding to the CBP/p300 and cdk9/cyclin T1 complexes facilitating transcription initiation...
  21. Chou S, Upton H, Bao K, Schulze Gahmen U, Samelson A, He N, et al. HIV-1 Tat recruits transcription elongation factors dispersed along a flexible AFF4 scaffold. Proc Natl Acad Sci U S A. 2013;110:E123-31 pubmed publisher
    ..Direct binding partners CycT1, ELL2, and ENL or AF9 act as bridging components that link this complex to two major elongation factors, P-TEFb ..
  22. 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
    ..Our data indicate that the various subunits of the human P-TEFb complex may play distinct roles at multiple stages to mediate Tat activation of HIV-1 transcription elongation. ..
  23. 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
  24. Wang Y, Liu X, De Clercq E. Role of the HIV-1 positive elongation factor P-TEFb and inhibitors thereof. Mini Rev Med Chem. 2009;9:379-85 pubmed
    ..elongation factor P-TEFb, a heterodimer containing a catalytic subunit (CDK9) and unique regulatory cyclins (CycT1), is required for HIV-1 Tat transcriptional activation...
  25. 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. ..
  26. Kuzmina A, Hadad U, Fujinaga K, Taube R. Functional characterization of a human cyclin T1 mutant reveals a different binding surface for Tat and HEXIM1. Virology. 2012;426:152-61 pubmed publisher
    ..of elongation by the viral Tat protein and the cellular positive transcription elongation factor b (P-TEFb; Cdk9/cyclin T1)...
  27. Kim Y, Bourgeois C, Isel C, Churcher M, Karn J. Phosphorylation of the RNA polymerase II carboxyl-terminal domain by CDK9 is directly responsible for human immunodeficiency virus type 1 Tat-activated transcriptional elongation. Mol Cell Biol. 2002;22:4622-37 pubmed
    ..assays with synthetic peptides showed that Tat activated CDK9 directly since the enzyme and its cyclin partner, cyclin T1, were present at equivalent levels in transcription complexes prepared in the presence or absence of Tat...
  28. 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
    b>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...
  29. Liou L, Herrmann C, Rice A. HIV-1 infection and regulation of Tat function in macrophages. Int J Biochem Cell Biol. 2004;36:1767-75 pubmed
    ..The viral Tat protein, whose function is mediated by the cellular cyclin T1 protein complexed with CDK9, is required for efficient transcription of the integrated HIV-1 provirus by RNA ..
  30. Fujinaga K, Cujec T, Peng J, Garriga J, Price D, Grana X, et al. The ability of positive transcription elongation factor B to transactivate human immunodeficiency virus transcription depends on a functional kinase domain, cyclin T1, and Tat. J Virol. 1998;72:7154-9 pubmed
    ..The kinase activity of CDK9 and cyclin T1 is essential for these effects. Moreover, P-TEFb binds to TAR only in the presence of Tat...
  31. 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...
  32. 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
    ..As such, targeting of Tat protein (and/or cellular cofactors) provide an interesting perspective for therapeutic intervention in the HIV replicative cycle and may afford lifetime control of the HIV infection. ..
  33. 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
    ..These results suggest that acetylation of CDK9 is an important posttranslational modification that is involved in regulating P-TEFb transcriptional elongation function. ..
  34. Biglione S, Byers S, Price J, Nguyen V, Bensaude O, Price D, et al. Inhibition of HIV-1 replication by P-TEFb inhibitors DRB, seliciclib and flavopiridol correlates with release of free P-TEFb from the large, inactive form of the complex. Retrovirology. 2007;4:47 pubmed
    The positive transcription elongation factor, P-TEFb, comprised of cyclin dependent kinase 9 (Cdk9) and cyclin T1, T2 or K regulates the productive elongation phase of RNA polymerase II (Pol II) dependent transcription of cellular and ..
  35. Dames S, Schönichen A, Schulte A, Barboric M, Peterlin B, Grzesiek S, et al. Structure of the Cyclin T binding domain of Hexim1 and molecular basis for its recognition of P-TEFb. Proc Natl Acad Sci U S A. 2007;104:14312-7 pubmed
    ..It directly binds to Cyclin T1 of P-TEFb and inhibits the kinase activity of Cdk9, leading to an arrest of transcription elongation...
  36. Chiang K, Sung T, Rice A. Regulation of cyclin T1 and HIV-1 Replication by microRNAs in resting CD4+ T lymphocytes. J Virol. 2012;86:3244-52 pubmed publisher
    The replication of integrated human immunodeficiency virus type 1 (HIV-1) is dependent on the cellular cofactor cyclin T1, which binds the viral Tat protein and activates the RNA polymerase II transcription of the integrated provirus...
  37. Bieniasz P, Grdina T, Bogerd H, Cullen B. Recruitment of a protein complex containing Tat and cyclin T1 to TAR governs the species specificity of HIV-1 Tat. EMBO J. 1998;17:7056-65 pubmed
    Human cyclin T1 (hCycT1), a major subunit of the essential elongation factor P-TEFb, has been proposed to act as a cofactor for human immunodeficiency virus type 1 (HIV-1) Tat...
  38. Zhang F, Barboric M, Blackwell T, Peterlin B. A model of repression: CTD analogs and PIE-1 inhibit transcriptional elongation by P-TEFb. Genes Dev. 2003;17:748-58 pubmed
    The positive transcription elongation factor b (P-TEFb) contains cyclin T1 (CycT1) and cyclin-dependent kinase 9 (Cdk9)...
  39. Napolitano G, Majello B, Lania L. Catalytic activity of Cdk9 is required for nuclear co-localization of the Cdk9/cyclin T1 (P-TEFb) complex. J Cell Physiol. 2003;197:1-7 pubmed
    Cdk9 and its binding partner cyclin T1 comprise the positive elongation factor b (P-TEFb). P-TEFb phosphorylates the RNA polymerase II carboxyl-terminal-domain (CTD) allowing efficient transcription elongation...
  40. Feichtinger S, Stamminger T, Müller R, Graf L, Klebl B, Eickhoff J, et al. Recruitment of cyclin-dependent kinase 9 to nuclear compartments during cytomegalovirus late replication: importance of an interaction between viral pUL69 and cyclin T1. J Gen Virol. 2011;92:1519-31 pubmed publisher
    ..Here, specific aspects of the mode of interaction between CDK9/cyclin T1 and pUL69 are described...
  41. Mbonye U, Karn J. Control of HIV latency by epigenetic and non-epigenetic mechanisms. Curr HIV Res. 2011;9:554-67 pubmed
  42. Wittmann B, Fujinaga K, Deng H, Ogba N, Montano M. The breast cell growth inhibitor, estrogen down regulated gene 1, modulates a novel functional interaction between estrogen receptor alpha and transcriptional elongation factor cyclin T1. Oncogene. 2005;24:5576-88 pubmed
    ..was recently shown to inhibit the positive transcription elongation factor b (P-TEFb) by interacting with the cyclin T1 subunit...
  43. Sung T, Rice A. Effects of prostratin on Cyclin T1/P-TEFb function and the gene expression profile in primary resting CD4+ T cells. Retrovirology. 2006;3:66 pubmed
    ..We examined resting CD4+ T cells from healthy donors to determine if prostratin induces Cyclin T1/P-TEFb, a cellular kinase composed of Cyclin T1 and Cyclin-dependent kinase-9 (CDK9) that mediates Tat function...
  44. Barboric M, Yik J, Czudnochowski N, Yang Z, Chen R, Contreras X, et al. Tat competes with HEXIM1 to increase the active pool of P-TEFb for HIV-1 transcription. Nucleic Acids Res. 2007;35:2003-12 pubmed
    ..Consisting of cyclin dependent kinase 9 (Cdk9) and cyclin T1, P-TEFb phosphorylates RNA polymerase II and the negative transcription elongation factor to stimulate the ..
  45. Baumli S, Lolli G, Lowe E, Troiani S, Rusconi L, Bullock A, et al. The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol and regulation by phosphorylation. EMBO J. 2008;27:1907-18 pubmed publisher
    ..the regulation of a transcriptional CDK by its cognate cyclin, we have determined the structures of the CDK9/CycT1 and free cyclin T2...
  46. He N, Liu M, Hsu J, Xue Y, Chou S, Burlingame A, et al. 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;38:428-38 pubmed publisher
    ..The ability of Tat to enable two different classes of elongation factors to cooperate and coordinate their actions on the same polymerase enzyme explains why Tat is such a powerful activator of HIV-1 transcription. ..
  47. Hoque M, Shamanna R, Guan D, PE ERY T, Mathews M. HIV-1 replication and latency are regulated by translational control of cyclin T1. J Mol Biol. 2011;410:917-32 pubmed publisher
    ..During viral replication, P-TEFb is recruited via interactions of its cyclin T1 subunit with the HIV Tat (transactivator of transcription) protein and TAR (transactivation response) element...
  48. 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...
  49. Taube R, Lin X, Irwin D, Fujinaga K, Peterlin B. Interaction between P-TEFb and the C-terminal domain of RNA polymerase II activates transcriptional elongation from sites upstream or downstream of target genes. Mol Cell Biol. 2002;22:321-31 pubmed
    ..P-TEFb is composed of Cdk9 and C-type cyclin T1 (CycT1), CycT2a, CycT2b, or CycK. The role of the C-terminal region of CycT1 and CycT2 remains unknown...
  50. 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. ..
  51. 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...
  52. 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. ..
  53. 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
    ..Therefore, it is likely that P-TEFb participates in regulation of elongation by RNA Pol II by phosphorylation of its substrates, hSPT5 and the CTD of RNA Pol II, in a CAK-independent manner. ..
  54. 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
    ..Thus, the phosphorylated P-TEFb is tagged for inhibition through association with 7SK. We discuss the implications of this mechanism in controlling P-TEFb activity during normal and stress-induced transcription. ..
  55. Das C, Edgcomb S, Peteranderl R, Chen L, Frankel A. Evidence for conformational flexibility in the Tat-TAR recognition motif of cyclin T1. Virology. 2004;318:306-17 pubmed
    b>Cyclin T1 (CycT1) is a cellular transcription elongation factor that also participates in Tat-mediated activation of several lentiviral promoters...
  56. Barboric M, Kohoutek J, Price J, Blazek D, Price D, Peterlin B. Interplay between 7SK snRNA and oppositely charged regions in HEXIM1 direct the inhibition of P-TEFb. EMBO J. 2005;24:4291-303 pubmed
    ..We propose a model where the interplay between 7SK snRNA and oppositely charged regions in HEXIM1 direct its binding to P-TEFb and subcellular localization that culminates in the inhibition of transcription. ..
  57. Anand K, Schulte A, Fujinaga K, Scheffzek K, Geyer M. Cyclin box structure of the P-TEFb subunit cyclin T1 derived from a fusion complex with EIAV tat. J Mol Biol. 2007;370:826-36 pubmed
    ..Its cyclin T1 subunit forms a ternary complex with the viral transcriptional transactivator (Tat) protein and the ..
  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. D Orso I, Frankel A. Tat acetylation modulates assembly of a viral-host RNA-protein transcription complex. Proc Natl Acad Sci U S A. 2009;106:3101-6 pubmed publisher
    ..ribonucleoprotein complex with transactivating responsive (TAR) RNA and P-TEFb, an elongation factor composed of cyclin T1 (CycT1) and Cdk9 that phosphorylates the C-terminal domain of RNA polymerase II...
  60. 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. ..
  61. McNamara R, McCann J, Gudipaty S, D ORSO I. Transcription factors mediate the enzymatic disassembly of promoter-bound 7SK snRNP to locally recruit P-TEFb for transcription elongation. Cell Rep. 2013;5:1256-68 pubmed publisher
    ..Recruitment of PPM1G to promoter-assembled 7SK snRNP provides a paradigm for rapid gene activation through transcriptional pause release. ..
  62. 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...
  63. Sun J, Soos T, Kewalramani V, Osiecki K, Zheng J, Falkin L, et al. CD4-specific transgenic expression of human cyclin T1 markedly increases human immunodeficiency virus type 1 (HIV-1) production by CD4+ T lymphocytes and myeloid cells in mice transgenic for a provirus encoding a monocyte-tropic HIV-1 isolate. J Virol. 2006;80:1850-62 pubmed
    ..Tat provides transcriptional activation critical for efficient HIV-1 replication by interacting with cyclin T1 and recruiting P-TEFb to efficiently elongate the nascent HIV transcript...
  64. 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
    ..of the human immunodeficiency (HIV) viral transcript associates with the viral protein Tat that in turn binds cyclin T1 and recruits active P-TEFb to the HIV promoter...
  65. 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
    ..P-TEFb complex containing HIV-1 Tat, human Cdk9 (also known as CDK9), and human cyclin T1 (also known as CCNT1)...
  66. 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. ..
  67. 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
    ..This restriction was mapped to interactions between Tat and TAR. Recently, human cyclin T1 was found to increase the binding of Tat to TAR and levels of Tat transactivation in rodent cells...
  68. 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
  69. Imai K, Asamitsu K, Victoriano A, Cueno M, Fujinaga K, Okamoto T. Cyclin T1 stabilizes expression levels of HIV-1 Tat in cells. FEBS J. 2009;276:7124-33 pubmed publisher
    Transcription from HIV-1 proviral DNA is a rate-determining step for HIV-1 replication. Interaction between the cyclin T1 (CycT1) subunit of positive transcription elongation factor b (P-TEFb) and the Tat transactivator protein of HIV-1 ..
  70. 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
    ..By increasing the affinity of the HIV-encoded transactivating (Tat) protein for CycT1, AFF1 facilitates Tat's extraction of P-TEFb from 7SK snRNP and the formation of Tat-SECs for HIV transcription...
  71. 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
  72. 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
    HIV-1 Tat activates transcription through binding to human cyclin T1, a regulatory subunit of the TAK/P-TEFb CTD kinase complex...
  73. 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
    Human cyclin T1 markedly stimulates tat-activation in rodent cells which are normally poorly responsive to the effects of Tat...
  74. 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. ..
  75. 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
  76. Liou L, Haaland R, Herrmann C, Rice A. Cyclin T1 but not cyclin T2a is induced by a post-transcriptional mechanism in PAMP-activated monocyte-derived macrophages. J Leukoc Biol. 2006;79:388-96 pubmed
    ..These complexes contain cyclin-dependent kinase 9 as the catalytic subunit and different cyclin subunits-cyclin T1, T2a, T2b, or K...
  77. 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. ..
  78. Kuzmina A, Verstraete N, Galker S, Maatook M, Bensaude O, Taube R. A single point mutation in cyclin T1 eliminates binding to Hexim1, Cdk9 and RNA but not to AFF4 and enforces repression of HIV transcription. Retrovirology. 2014;11:51 pubmed publisher
    ..To map residues in the cyclin box of cyclin T1 that mediate the binding of P-TEFb to its interacting host partners and support HIV transcription, a pool of N-..
  79. 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
    ..These observations strengthen the proposal that the mechanism of action of Tat involves the recruitment or activation of TAK, resulting in activated transcription through phosphorylation of the CTD. ..
  80. Peng J, Zhu Y, Milton J, Price D. Identification of multiple cyclin subunits of human P-TEFb. Genes Dev. 1998;12:755-62 pubmed
    ..Cyclin T2 has two forms (T2a and T2b) because of alternative splicing. Both cyclin T1 and T2 are ubiquitously expressed...
  81. Young T, Wang Q, PE ERY T, Mathews M. The human I-mfa domain-containing protein, HIC, interacts with cyclin T1 and modulates P-TEFb-dependent transcription. Mol Cell Biol. 2003;23:6373-84 pubmed
    ..The cyclin T1 subunit of P-TEFb engages cellular transcription factors as well as the human immunodeficiency virus type 1 (HIV-..
  82. 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
    c-Myc promotes cellular proliferation, sensitizes cells to apoptosis and prevents differentiation. It binds cyclin T1 structurally and functionally from the positive transcription elongation factor b (P-TEFb)...
  83. Mueller D, Bach C, Zeisig D, Garcia Cuellar M, Monroe S, Sreekumar A, et al. A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification. Blood. 2007;110:4445-54 pubmed
    ..According to structure-function data, DOT1L recruitment was important for transformation by the MLL-ENL fusion derivative. These results suggest a function of ENL in histone modification and transcriptional elongation. ..
  84. 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
    ..elongation factor b (P-TEFb) is a heterodimeric complex composed of cyclin-dependent kinase 9 and its regulator cyclin T1/2...
  85. 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...
  86. 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. ..
  87. 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. ..
  88. Verstraete N, Kuzmina A, Diribarne G, Nguyen V, Kobbi L, Ludanyi M, et al. A Cyclin T1 point mutation that abolishes positive transcription elongation factor (P-TEFb) binding to Hexim1 and HIV tat. Retrovirology. 2014;11:50 pubmed publisher
    ..It is recruited to the HIV LTR promoter through an interaction between the Tat viral protein and its Cyclin T1 subunit...
  89. 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
    ..Moreover, overexpression of human cyclin T rescues Tat activity in nonpermissive rodent cells. We propose that Tat directs cyclin T-CDK9 to RNAPII through cooperative binding to TAR RNA. ..
  90. 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
    ..These results indicate that a PITALRE-containing complex mediates transactivation by Tat and suggest that Tat proteins function by localizing such a PITALRE-containing complex to the site of the transcribing provirus...
  91. Chen D, Fong Y, Zhou Q. Specific interaction of Tat with the human but not rodent P-TEFb complex mediates the species-specific Tat activation of HIV-1 transcription. Proc Natl Acad Sci U S A. 1999;96:2728-33 pubmed
    ..Human P-TEFb, composed of Cdk9 and cyclin T1, is a general transcription elongation factor that phosphorylates the C-terminal domain of RNA polymerase II...
  92. Marcello A, Zoppe M, Giacca M. Multiple modes of transcriptional regulation by the HIV-1 Tat transactivator. IUBMB Life. 2001;51:175-81 pubmed
    ..Increase 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 ..