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. 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
  2. Barboric M, Lenasi T. Kick-sTARting HIV-1 transcription elongation by 7SK snRNP deporTATion. Nat Struct Mol Biol. 2010;17:928-30 pubmed publisher
    ..The HIV-1 Tat protein promotes viral transcription elongation by recruiting P-TEFb to RNA element TAR on the viral mRNA. Recent work from D'Orso and Frankel uncovers unexpected aspects of this process. ..
  3. Li Z, Guo J, Wu Y, Zhou Q. The BET bromodomain inhibitor JQ1 activates HIV latency through antagonizing Brd4 inhibition of Tat-transactivation. Nucleic Acids Res. 2013;41:277-87 pubmed publisher
  4. 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
    ..Transfection experiments with wild-type or kinase knockout PITALRE demonstrated that P-TEFb is required for Tat function. Our results suggest that P-TEFb represents an attractive target for the development of novel HIV therapeutics. ..
  5. 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
    Transcription of the human immunodeficiency virus type 1 (HIV) requires the interaction of the cyclin T1 (CycT1) subunit of a host cellular factor, the positive transcription elongation factor b (P-TEFb), with the viral Tat protein, at ..
  6. Schulte A, Czudnochowski N, Barboric M, Schönichen A, Blazek D, Peterlin B, et al. Identification of a cyclin T-binding domain in Hexim1 and biochemical analysis of its binding competition with HIV-1 Tat. J Biol Chem. 2005;280:24968-77 pubmed
    ..5-kDa size that binds the cyclin boxes of Cyclin T1. Functional assays in HeLa cells showed that this cyclin T-binding domain (TBD) is required for the binding of ..
  7. Rechter S, Scott G, Eickhoff J, Zielke K, Auerochs S, Müller R, et al. Cyclin-dependent Kinases Phosphorylate the Cytomegalovirus RNA Export Protein pUL69 and Modulate Its Nuclear Localization and Activity. J Biol Chem. 2009;284:8605-13 pubmed publisher
    ..The CDK9 and cyclin T1 proteins colocalized with these pUL69 aggregates, whereas other CDKs behaved differently...
  8. Michels A, Nguyen V, Fraldi A, Labas V, Edwards M, Bonnet F, et al. MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner. Mol Cell Biol. 2003;23:4859-69 pubmed
    ..P-TEFb is essential for transcriptional elongation in human cells. A highly specific interaction among cyclin T1, the viral protein Tat, and the transactivation response (TAR) element RNA determines the productive ..
  9. Mbonye U, Gokulrangan G, Datt M, Dobrowolski C, Cooper M, Chance M, et al. Phosphorylation of CDK9 at Ser175 enhances HIV transcription and is a marker of activated P-TEFb in CD4(+) T lymphocytes. PLoS Pathog. 2013;9:e1003338 pubmed publisher
    ..occurs during TCR activation of primary resting memory CD4+ T cells together with upregulation of the Cyclin T1 regulatory subunit of P-TEFb, and Thr186 phosphorylation of CDK9...

More Information

Publications143 found, 100 shown here

  1. 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. ..
  2. 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
    ..In this study, we examined the subcellular distribution of Cdk9 and cyclin T1 using high resolution immunofluorescence microscopy and found that Cdk9 and cyclin T1 localized throughout the ..
  3. Rice A, Herrmann C. Regulation of TAK/P-TEFb in CD4+ T lymphocytes and macrophages. Curr HIV Res. 2003;1:395-404 pubmed
    ..for HIV replication and requires a cellular protein kinase activity termed TAK/P-TEFb, composed of CDK9 and cyclin T1, for its transactivation function...
  4. Brès V, Gomes N, Pickle L, Jones K. A human splicing factor, SKIP, associates with P-TEFb and enhances transcription elongation by HIV-1 Tat. Genes Dev. 2005;19:1211-26 pubmed
    ..SKIP associates with CycT1:CDK9/P-TEFb and Tat:P-TEFb complexes in nuclear extracts and interacts with recombinant Tat:P-TEFb:TAR RNA ..
  5. 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--Pol II ..
  6. Gu J, Babayeva N, Suwa Y, Baranovskiy A, Price D, Tahirov T. Crystal structure of HIV-1 Tat complexed with human P-TEFb and AFF4. Cell Cycle. 2014;13:1788-97 pubmed publisher
    ..determined the crystal structure of the Tat•AFF4•P-TEFb complex containing HIV-1 Tat (residues 1-48), human Cyclin T1 (1-266), human Cdk9 (7-332), and human AFF4 (27-69)...
  7. Herrmann C, Carroll R, Wei P, Jones K, Rice A. Tat-associated kinase, TAK, activity is regulated by distinct mechanisms in peripheral blood lymphocytes and promonocytic cell lines. J Virol. 1998;72:9881-8 pubmed
    ..of TAK has been identified as cyclin-dependent kinase Cdk9, and its regulatory partner has been identified as cyclin T1; these proteins are also components of positive transcription elongation factor P-TEFb...
  8. Marcello A, Cinelli R, Ferrari A, Signorelli A, Tyagi M, Pellegrini V, et al. Visualization of in vivo direct interaction between HIV-1 TAT and human cyclin T1 in specific subcellular compartments by fluorescence resonance energy transfer. J Biol Chem. 2001;276:39220-5 pubmed
    Human cyclin T1, a component of the P-TEFb kinase complex, was originally identified through its biochemical interaction with the Tat transactivator protein of human immunodeficiency virus type 1 (HIV-1)...
  9. Liou L, Herrmann C, Rice A. Transient induction of cyclin T1 during human macrophage differentiation regulates human immunodeficiency virus type 1 Tat transactivation function. J Virol. 2002;76:10579-87 pubmed
    ..and stimulates transcription of the integrated provirus by recruiting the kinase complex TAK/P-TEFb, composed of cyclin T1 (CycT1) and Cdk9, to the viral TAR RNA element...
  10. Yokoyama A, Lin M, Naresh A, Kitabayashi I, Cleary M. A higher-order complex containing AF4 and ENL family proteins with P-TEFb facilitates oncogenic and physiologic MLL-dependent transcription. Cancer Cell. 2010;17:198-212 pubmed publisher
    ..Thus, AEP recruitment is an integral part of both physiological and pathological MLL-dependent transcriptional pathways. Bypass of its normal recruitment mechanisms is the strategy most frequently used by MLL oncoproteins. ..
  11. Isel C, Karn J. Direct evidence that HIV-1 Tat stimulates RNA polymerase II carboxyl-terminal domain hyperphosphorylation during transcriptional elongation. J Mol Biol. 1999;290:929-41 pubmed
    ..Immunoblotting experiments have shown that CDK9 and its associated cyclin, cyclin T1, are present at equivalent levels in both the pre-initiation and elongation complexes...
  12. 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 stimulating the Tat-activated kinase (TAK/p-TEFb), a protein kinase composed of CDK9 and its cyclin partner, cyclin T1. CDK9 is able to hyperphosphorylate the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase ..
  13. De Luca A, De Falco M, Baldi A, Paggi M. Cyclin T: three forms for different roles in physiological and pathological functions. J Cell Physiol. 2003;194:101-7 pubmed
    ..There are three forms of cyclin T: cyclin T1, cyclin T2a, and T2b...
  14. Loregian A, Bortolozzo K, Boso S, Caputo A, Palu G. Interaction of Sp1 transcription factor with HIV-1 Tat protein: looking for cellular partners. FEBS Lett. 2003;543:61-5 pubmed
    ..which cellular proteins recently shown to play a relevant role in Tat function, namely TATA box-binding protein, cyclin T1, CDK9, and cyclin T1/CDK9 complex, were coexpressed, individually or in pair-wise combination, with Tat and Sp1 ..
  15. Wang Y, Rice A. Interleukin-10 inhibits HIV-1 LTR-directed gene expression in human macrophages through the induction of cyclin T1 proteolysis. Virology. 2006;352:485-92 pubmed
    ..MDMs) in a manner that correlates with the early induction and subsequent shut-off of its cellular cofactor cyclin T1. Here, we report that IL-10 down-regulates cyclin T1 expression through the induction of proteasome-mediated ..
  16. Ott M, Geyer M, Zhou Q. The control of HIV transcription: keeping RNA polymerase II on track. Cell Host Microbe. 2011;10:426-35 pubmed publisher
    Thirteen years ago, human cyclin T1 was identified as part of the positive transcription elongation factor b (P-TEFb) and the long-sought host cofactor for the HIV-1 transactivator Tat...
  17. 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...
  18. 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 ..
  19. 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...
  20. 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. ..
  21. Barboric M, Peterlin B. A new paradigm in eukaryotic biology: HIV Tat and the control of transcriptional elongation. PLoS Biol. 2005;3:e76 pubmed
  22. 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...
  23. 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...
  24. 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...
  25. 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 ..
  26. 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. ..
  27. 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...
  28. 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. ..
  29. 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...
  30. 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. ..
  31. 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...
  32. 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. ..
  33. 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)...
  34. 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. ..
  35. 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
  36. 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. ..
  37. 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. ..
  38. 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)...
  39. 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 ..
  40. 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...
  41. 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...
  42. 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...
  43. 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. ..
  44. 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)...
  45. 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...
  46. 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 ..
  47. 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. ..
  48. 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
  49. 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...
  50. 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. ..
  51. 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)...
  52. 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...
  53. 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...
  54. 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 ..
  55. 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...
  56. 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...
  57. 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. ..
  58. 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. ..
  59. 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 ..
  60. 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...
  61. 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...
  62. 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...
  63. 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)...
  64. 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...
  65. 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...
  66. Mbonye U, Karn J. Control of HIV latency by epigenetic and non-epigenetic mechanisms. Curr HIV Res. 2011;9:554-67 pubmed
  67. 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...
  68. 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...
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    ..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 ..
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    ..the regulation of a transcriptional CDK by its cognate cyclin, we have determined the structures of the CDK9/CycT1 and free cyclin T2...
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    ..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. ..
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    ..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...
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    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...
  74. 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...
  75. 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. ..
  76. 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...
  77. 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. ..
  78. 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. ..
  79. 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. ..
  80. 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...
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    ..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. ..
  82. 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 ..
  83. 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. ..
  84. 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...
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    ..Finally, we cover recent literature on viral microRNAs which have been shown to alter chromatin structure by inducing methylation or even by remodeling nucleosomes. ..
  86. 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. ..
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    ..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...
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    ..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...
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    ..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...
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    ..P-TEFb complex containing HIV-1 Tat, human Cdk9 (also known as CDK9), and human cyclin T1 (also known as CCNT1)...
  91. 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. ..
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    ..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...