cdk9

Summary

Gene Symbol: cdk9
Description: cyclin-dependent kinase 9
Alias: C-2k, CDC2L4, CTK1, PITALRE, TAK, 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

Top Publications

  1. pmc HIV-1 Tat and host AFF4 recruit two transcription elongation factors into a bifunctional complex for coordinated activation of HIV-1 transcription
    Nanhai He
    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
    Mol Cell 38:428-38. 2010
  2. ncbi Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4
    Zhiyuan Yang
    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA
    Mol Cell 19:535-45. 2005
  3. ncbi A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA
    P Wei
    Regulatory Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037 1099, USA
    Cell 92:451-62. 1998
  4. pmc Transcriptional and posttranscriptional regulation of HIV-1 gene expression
    Jonathan Karn
    Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Cold Spring Harb Perspect Med 2:a006916. 2012
  5. ncbi The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription
    Z Yang
    Department of Molecular and Cell Biology, University of California at Berkeley, USA
    Nature 414:317-22. 2001
  6. pmc Crystal structure of HIV-1 Tat complexed with human P-TEFb
    Tahir H Tahirov
    Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198 7696, USA
    Nature 465:747-51. 2010
  7. pmc Cyclin-dependent kinase control of the initiation-to-elongation switch of RNA polymerase II
    Stephane Larochelle
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York, USA
    Nat Struct Mol Biol 19:1108-15. 2012
  8. pmc Evidence that P-TEFb alleviates the negative effect of DSIF on RNA polymerase II-dependent transcription in vitro
    T Wada
    Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta cho, Midori ku, Yokohama 226 8501, Japan
    EMBO J 17:7395-403. 1998
  9. pmc The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol and regulation by phosphorylation
    Sonja Baumli
    Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, Oxford, UK
    EMBO J 27:1907-18. 2008
  10. pmc Characterization of Cdk9 T-loop phosphorylation in resting and activated CD4(+) T lymphocytes
    Rajesh Ramakrishnan
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Leukoc Biol 86:1345-50. 2009

Detail Information

Publications257 found, 100 shown here

  1. pmc HIV-1 Tat and host AFF4 recruit two transcription elongation factors into a bifunctional complex for coordinated activation of HIV-1 transcription
    Nanhai He
    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
    Mol Cell 38:428-38. 2010
    ..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...
  2. ncbi Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4
    Zhiyuan Yang
    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA
    Mol Cell 19:535-45. 2005
    The cyclinT1/Cdk9 heterodimer that constitutes core P-TEFb is generally presumed to be the transcriptionally active form for stimulating RNA polymerase II elongation...
  3. ncbi A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA
    P Wei
    Regulatory Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037 1099, USA
    Cell 92:451-62. 1998
    ..Cyclin T is a partner for CDK9, an RNAPII transcription elongation factor...
  4. pmc Transcriptional and posttranscriptional regulation of HIV-1 gene expression
    Jonathan Karn
    Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Cold Spring Harb Perspect Med 2:a006916. 2012
    ..In cells that are not fully activated, limiting levels of Tat and Rev act as potent blocks to premature virus production...
  5. ncbi The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription
    Z Yang
    Department of Molecular and Cell Biology, University of California at Berkeley, USA
    Nature 414:317-22. 2001
    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...
  6. pmc Crystal structure of HIV-1 Tat complexed with human P-TEFb
    Tahir H Tahirov
    Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198 7696, USA
    Nature 465:747-51. 2010
    ..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)...
  7. pmc Cyclin-dependent kinase control of the initiation-to-elongation switch of RNA polymerase II
    Stephane Larochelle
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York, USA
    Nat Struct Mol Biol 19:1108-15. 2012
    ..Pause release depends on Cdk9-cyclin T1 (P-TEFb); Cdk7 is also required for Cdk9-activating phosphorylation and Cdk9-dependent downstream events--..
  8. pmc Evidence that P-TEFb alleviates the negative effect of DSIF on RNA polymerase II-dependent transcription in vitro
    T Wada
    Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta cho, Midori ku, Yokohama 226 8501, Japan
    EMBO J 17:7395-403. 1998
    ..b>PITALRE, a member of the Cdc2 family of protein kinases, is the catalytic subunit of P-TEFb...
  9. pmc The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol and regulation by phosphorylation
    Sonja Baumli
    Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, Oxford, UK
    EMBO J 27:1907-18. 2008
    The positive transcription elongation factor b (P-TEFb) (CDK9/cyclin T (CycT)) promotes mRNA transcriptional elongation through phosphorylation of elongation repressors and RNA polymerase II...
  10. pmc Characterization of Cdk9 T-loop phosphorylation in resting and activated CD4(+) T lymphocytes
    Rajesh Ramakrishnan
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Leukoc Biol 86:1345-50. 2009
    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...
  11. ncbi Analysis of the large inactive P-TEFb complex indicates that it contains one 7SK molecule, a dimer of HEXIM1 or HEXIM2, and two P-TEFb molecules containing Cdk9 phosphorylated at threonine 186
    Qintong Li
    Department of Biochemistry and Molecular Biology Program, University of Iowa, Iowa City, Iowa 52242, USA
    J Biol Chem 280:28819-26. 2005
    ..HEXIM.P-TEFb complex. Analysis of T-loop phosphorylation in Cdk9 indicated that phosphorylation of Thr(186), but not Ser(175), was essential for kinase activity and for recruitment ..
  12. pmc 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
    Jasper H N Yik
    Department of Molecular and Cellular Biology, University of California, Berkeley, 94720, USA
    Mol Cell Biol 24:5094-105. 2004
    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...
  13. pmc Conserved P-TEFb-interacting domain of BRD4 inhibits HIV transcription
    Dwayne A Bisgrove
    Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94158, USA
    Proc Natl Acad Sci U S A 104:13690-5. 2007
    ..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...
  14. pmc P-TEFb kinase is required for HIV Tat transcriptional activation in vivo and in vitro
    H S Mancebo
    Tularik, Inc, South San Francisco, California 94080 USA
    Genes Dev 11:2633-44. 1997
    ..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...
  15. pmc Chromatin dynamics associated with HIV-1 Tat-activated transcription
    Rebecca Easley
    The George Washington University Medical Center, Department of Microbiology, Immunology, and Tropical Medicine, Washington, DC 20037, USA
    Biochim Biophys Acta 1799:275-85. 2010
    ..Finally, we cover recent literature on viral microRNAs which have been shown to alter chromatin structure by inducing methylation or even by remodeling nucleosomes...
  16. pmc A higher-order complex containing AF4 and ENL family proteins with P-TEFb facilitates oncogenic and physiologic MLL-dependent transcription
    Akihiko Yokoyama
    National Cancer Center Research Institute, Tokyo, Japan
    Cancer Cell 17:198-212. 2010
    ..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...
  17. pmc The CDC2-related kinase PITALRE is the catalytic subunit of active multimeric protein complexes
    J Garriga
    Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA
    Biochem J 319:293-8. 1996
    b>PITALRE is a human protein kinase identified by means of its partial sequence identity to the cell division cycle regulatory kinase CDC2...
  18. pmc Varying modulation of HIV-1 LTR activity by Baf complexes
    Rachel Van Duyne
    Department of Molecular and Microbiology, National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA 20110, USA
    J Mol Biol 411:581-96. 2011
    ..Additionally, cdk9/cyclin T in the presence of Tat is able to phosphorylate Baf53 in vitro, implying that this posttranslationally ..
  19. pmc CDK9 directs H2B monoubiquitination and controls replication-dependent histone mRNA 3'-end processing
    Judith Pirngruber
    Department of Molecular Oncology, Göttingen Center for Molecular Biosciences, University of Gottingen, Gottingen, Germany
    EMBO Rep 10:894-900. 2009
    ..Cyclin-dependent kinase 9 (CDK9) regulates gene expression by phosphorylating transcriptional regulatory proteins, including the RNA polymerase II ..
  20. pmc HIV latency
    Robert F Siliciano
    Department of Medicine, Johns Hopkins University School of Medicine, Howard Hughes Medical Institute, Baltimore, Maryland 21205, USA
    Cold Spring Harb Perspect Med 1:a007096. 2011
    ..Several approaches are under exploration for reactivating latent virus with the hope that this will allow elimination of the latent reservoir...
  21. doi Serine-7 but not serine-5 phosphorylation primes RNA polymerase II CTD for P-TEFb recognition
    Nadine Czudnochowski
    Max Planck Institut fur molekulare Physiologie, Abt Physikalische Biochemie, Otto Hahn Straße 11, 44227 Dortmund, Germany
    Nat Commun 3:842. 2012
    ..Inhibition of P-TEFb activity is mediated by two regions in Hexim1 that act synergistically on Cdk9 and Cyclin T1...
  22. pmc Phosphatase PPM1A regulates phosphorylation of Thr-186 in the Cdk9 T-loop
    Yan Wang
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 283:33578-84. 2008
    b>Cdk9 is the catalytic subunit of a general RNA polymerase II elongation factor known as positive transcription elongation factor b (P-TEFb)...
  23. pmc Tat-associated kinase, TAK, activity is regulated by distinct mechanisms in peripheral blood lymphocytes and promonocytic cell lines
    C H Herrmann
    Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Virol 72:9881-8. 1998
    ..The catalytic subunit 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 ..
  24. ncbi 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
    Y H Ping
    Department of Pharmacology, Robert Wood Johnson Medical School, and Molecular Biosciences Graduate Program at Rutgers University, Piscataway, New Jersey 08854, USA
    J Biol Chem 276:12951-8. 2001
    ..These findings reveal a molecular mechanism for the negative and positive regulation of transcriptional elongation at the HIV-1 promoter...
  25. pmc CDK9-dependent transcriptional elongation in the innate interferon-stimulated gene response to respiratory syncytial virus infection in airway epithelial cells
    Bing Tian
    Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA
    J Virol 87:7075-92. 2013
    ..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 ..
  26. pmc 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
    K Fujinaga
    Howard Hughes Medical Institute, Departments of Medicine, Microbiology, and Immunology, University of California, San Francisco, CA 94143 0703, USA
    Proc Natl Acad Sci U S A 96:1285-90. 1999
    ..These findings reveal the molecular basis for the restriction of Tat transactivation in rodent cells...
  27. ncbi Dual role of host cell factors in HIV-1 replication: restriction and enhancement of the viral cycle
    Mayte Coiras
    AIDS Immunopathology Unit, National Centre of Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
    AIDS Rev 12:103-12. 2010
    ..The increasing knowledge of viral protein interactions with host cell factors will be essential for the discovery of new targets that could be used to design new therapeutic strategies...
  28. pmc Novel HIV-1 therapeutics through targeting altered host cell pathways
    William Coley
    George Washington University, School of Medicine, Department of Microbiology, Immunology and Tropical Medicine, Washington, DC 20037, USA
    Expert Opin Biol Ther 9:1369-82. 2009
    ..can be accomplished either by using small molecules to alter the function of the host's proteins such as p53 or cdk9, or by utilizing new advances in siRNA therapies to knock down essential host factors such as CCR5 and CXCR4...
  29. pmc HIV-1 Vif promotes the G₁- to S-phase cell-cycle transition
    JiangFang Wang
    Division of Rheumatology, The Children s Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA
    Blood 117:1260-9. 2011
    ..Using mass spectrometry, we identified 2 novel cellular partners of Vif, Brd4 and Cdk9, both of which are known to regulate cell-cycle progression...
  30. pmc The structural biology of HIV-1: mechanistic and therapeutic insights
    Alan Engelman
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts 02215, USA
    Nat Rev Microbiol 10:279-90. 2012
    ..Here, we review recent advances in HIV-1 structural biology, focusing on the molecular mechanisms of viral replication and on the development of new therapeutics...
  31. ncbi Androgen receptor interacts with the positive elongation factor P-TEFb and enhances the efficiency of transcriptional elongation
    D K Lee
    George Whipple Laboratory for Cancer Research, Department of Pathology, Urology, Radiation Oncology, and the Cancer Center, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 276:9978-84. 2001
    ..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)...
  32. doi The ins and outs of HIV-1 Tat
    Solène Debaisieux
    CPBS, UMR 5236 CNRS, Universite de Montpellier, 1919 Route de Mende, 34923, Montpellier Cedex 05, France
    Traffic 13:355-63. 2012
    ..This review focuses on some of the recently identified molecular details underlying the unusual transcellular transport pathway used by Tat, such as the role of the single Trp in Tat for its membrane insertion and translocation...
  33. pmc Controlling cellular P-TEFb activity by the HIV-1 transcriptional transactivator Tat
    Lisa Muniz
    Laboratoire de Biologie Moleculaire Eucaryote du CNRS, UMR5099, IFR109 CNRS, Universite Paul Sabatier, Toulouse, France
    PLoS Pathog 6:e1001152. 2010
    ....
  34. pmc 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
    Eugene C Dow
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
    J Cell Physiol 224:84-93. 2010
    ..Core P-TEFb is comprised of Cdk9 and a cyclin regulatory subunit, with Cyclin T1 being the predominant Cdk9-associated cyclin...
  35. pmc Transcription elongation factor P-TEFb is required for HIV-1 tat transactivation in vitro
    Y Zhu
    Department of Biochemistry, University of Iowa, Iowa City, Iowa 52242 USA
    Genes Dev 11:2622-32. 1997
    ..Sequence comparison suggests that a protein with 72% identity, PITALRE, could be the human homolog of the Drosophila protein...
  36. pmc Cyclin T1 and CDK9 T-loop phosphorylation are downregulated during establishment of HIV-1 latency in primary resting memory CD4+ T cells
    Sona Budhiraja
    Department of Molecular Microbiology and Virology, Baylor College of Medicine, Houston, TX, USA
    J Virol 87:1211-20. 2013
    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...
  37. pmc PP2B and PP1alpha cooperatively disrupt 7SK snRNP to release P-TEFb for transcription in response to Ca2+ signaling
    Ruichuan Chen
    Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen 361005, Fujian, China
    Genes Dev 22:1356-68. 2008
    The positive transcription elongation factor b (P-TEFb), consisting of Cdk9 and cyclin T, stimulates RNA polymerase II elongation and cotranscriptional pre-mRNA processing...
  38. ncbi Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA
    Jasper H N Yik
    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
    Mol Cell 12:971-82. 2003
    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...
  39. pmc 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
    M E Garber
    Regulatory Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037 1099, USA
    Genes Dev 12:3512-27. 1998
    ..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...
  40. pmc SKIP interacts with c-Myc and Menin to promote HIV-1 Tat transactivation
    Vanessa Brès
    Regulatory Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037 1099, USA
    Mol Cell 36:75-87. 2009
    The Ski-interacting protein SKIP/SNW1 associates with the P-TEFb/CDK9 elongation factor and coactivates inducible genes, including HIV-1...
  41. pmc Role of cdk9 in the optimization of expression of the genes regulated by ICP22 of herpes simplex virus 1
    Lizette Olga Durand
    Marjorie B Kovler Viral Oncology Laboratories, The University of Chicago, Chicago, IL 60637, USA
    J Virol 82:10591-9. 2008
    ..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 ..
  42. ncbi Cooperative interaction between HIV-1 regulatory proteins Tat and Vpr modulates transcription of the viral genome
    B E Sawaya
    Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122, USA
    J Biol Chem 275:35209-14. 2000
    ..Because Tat utilizes cyclin T1 and its partner, CDK9 to elevate the level of transcription from the LTR, we examined the cooperativity between Vpr, Tat, and cyclin T1/..
  43. ncbi Heat shock protein 40 is necessary for human immunodeficiency virus-1 Nef-mediated enhancement of viral gene expression and replication
    Manish Kumar
    National Centre for Cell Science, Ganeshkhind, Pune 411007, India
    J Biol Chem 280:40041-50. 2005
    ..Thus our results clearly indicate that Hsp40 is crucial for Nef-mediated enhancement of viral gene expression and replication...
  44. pmc The BET bromodomain inhibitor JQ1 activates HIV latency through antagonizing Brd4 inhibition of Tat-transactivation
    Zichong Li
    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    Nucleic Acids Res 41:277-87. 2013
    ....
  45. pmc MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner
    Annemieke A Michels
    UMR 8541 CNRS, Ecole Normale Superieure, Laboratoire de Régulation de l Expression Génétique, 75230 Paris Cedex 05, France
    Mol Cell Biol 23:4859-69. 2003
    ..transcription elongation factor b (P-TEFb) comprises a cyclin (T1 or T2) and a kinase, cyclin-dependent kinase 9 (CDK9), which phosphorylates the carboxyl-terminal domain of RNA polymerase II...
  46. ncbi Multiple actions of the human immunodeficiency virus type-1 Tat protein on microglial cell functions
    Luisa Minghetti
    Department of Cell Biology and Neuroscience, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome, Italy
    Neurochem Res 29:965-78. 2004
    ....
  47. ncbi TFIIH inhibits CDK9 phosphorylation during human immunodeficiency virus type 1 transcription
    M Zhou
    Virus Tumor Biology Section, Basic Research Laboratory, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 276:44633-40. 2001
    ..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...
  48. doi Formation of Tat-TAR containing ribonucleoprotein complexes for biochemical and structural analyses
    Janna M Bigalke
    Max Planck Institut fur molekulare Physiologie, Abteilung Physikalische Biochemie, Otto Hahn Strasse 11, 44227 Dortmund, Germany
    Methods 53:78-84. 2011
    ..positive transcription elongation factor P-TEFb to recruit Cyclin T and its corresponding Cyclin-dependent kinase Cdk9 to the RNA polymerase II...
  49. pmc Binding of the 7SK snRNA turns the HEXIM1 protein into a P-TEFb (CDK9/cyclin T) inhibitor
    Annemieke A Michels
    UMR 8541 CNRS, Ecole Normale Superieure, Régulation de l Expression Génétique, Paris, France
    EMBO J 23:2608-19. 2004
    ..Core active P-TEFb is composed of CDK9 and cyclin T...
  50. pmc Identification of multiple cyclin subunits of human P-TEFb
    J Peng
    Department of Biochemistry, University of Iowa, Iowa City, Iowa 52242, USA
    Genes Dev 12:755-62. 1998
    ..Drosophila P-TEFb was identified recently as a cyclin-dependent kinase (CDK9) paired with a cyclin subunit (cyclin T)...
  51. pmc Cross-talk among RNA polymerase II kinases modulates C-terminal domain phosphorylation
    Ballachanda N Devaiah
    Experimental Immunology Branch, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 287:38755-66. 2012
    ..We report that three CTD kinases, CDK7, CDK9, and BRD4, engage in cross-talk, modulating their subsequent CTD phosphorylation...
  52. ncbi Acetylation of Tat defines a cyclinT1-independent step in HIV transactivation
    Katrin Kaehlcke
    Deutsches Krebsforschungszentrum, D 69120 Heidelberg, Germany
    Mol Cell 12:167-76. 2003
    ..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...
  53. pmc The control of HIV transcription: keeping RNA polymerase II on track
    Melanie Ott
    Gladstone Institutes of Virology and Immunology, University of California, San Francisco, 94158, USA
    Cell Host Microbe 10:426-35. 2011
    ....
  54. pmc Cyclin-dependent kinase-9 is a component of the p300/GATA4 complex required for phenylephrine-induced hypertrophy in cardiomyocytes
    Yoichi Sunagawa
    Division of Translational Research, Kyoto Medical Center, National Hospital Organization, 1 1 Mukaihata cho, Fukakusa, Fushimi ku, Kyoto, Japan
    J Biol Chem 285:9556-68. 2010
    ..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...
  55. pmc Acetylation of conserved lysines in the catalytic core of cyclin-dependent kinase 9 inhibits kinase activity and regulates transcription
    Arianna Sabò
    ICGEB Trieste, Molecular Medicine Laboratory, Padriciano, 99, 34012 Trieste, Italy
    Mol Cell Biol 28:2201-12. 2008
    ..function is P-TEFb (positive transcription elongation factor b), which is composed of cyclin-dependent kinase 9 (CDK9) associated with members of the cyclin T family...
  56. ncbi Cyclin-dependent kinase-9: an RNAPII kinase at the nexus of cardiac growth and death cascades
    Motoaki Sano
    Center for Cardiovascular Development, Baylor College of Medicine, Houston, TX 77030, USA
    Circ Res 95:867-76. 2004
    ..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...
  57. ncbi Role of the human and murine cyclin T proteins in regulating HIV-1 tat-activation
    Y T Kwak
    Division of Hematology Oncology, Department of Medicine, Harold Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, 75235 8594, USA
    J Mol Biol 288:57-69. 1999
    ..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...
  58. pmc Recruitment of a protein complex containing Tat and cyclin T1 to TAR governs the species specificity of HIV-1 Tat
    P D Bieniasz
    Howard Hughes Medical Institute and Department of Genetics, Box 3025, Room 426, CARL Building, Duke University Medical Center, Research Drive, Durham, NC 27710, USA
    EMBO J 17:7056-65. 1998
    ....
  59. pmc CDK2 regulates HIV-1 transcription by phosphorylation of CDK9 on serine 90
    Denitra Breuer
    Center for Sickle Cell Disease, Department of Medicine, Howard University, 1840 7th Street, N W HURB1, Suite 202, Washington, DC 20001, USA
    Retrovirology 9:94. 2012
    ..by the viral Tat protein that recruits host positive transcription elongation factor-b (P-TEFb) containing CDK9/cyclin T1 to the HIV-1 promoter...
  60. pmc Cyclin T1 expression is mediated by a complex and constitutively active promoter and does not limit human immunodeficiency virus type 1 Tat function in unstimulated primary lymphocytes
    Juan Martin-Serrano
    Aaron Diamond AIDS Research Center, Rockefeller University, New York, New York 10016, USA
    J Virol 76:208-19. 2002
    ..These results strongly suggest that CycT1 expression levels in unstimulated primary lymphocytes do not profoundly limit HIV-1 gene expression or provide an adequate mechanistic explanation for proviral latency in vivo...
  61. pmc Mutual information analysis reveals coevolving residues in Tat that compensate for two distinct functions in HIV-1 gene expression
    Siddharth S Dey
    Department of Chemical and Biomolecular Engineering and the Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, USA
    J Biol Chem 287:7945-55. 2012
    ....
  62. ncbi 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes
    V T Nguyen
    Genetique Moleculaire, UMR 8541 CNRS, Ecole Normale Superieure, 46 rue d Ulm, 75230 Paris Cedex 05, France
    Nature 414:322-5. 2001
    ..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)...
  63. ncbi Poly(ADP-ribose) polymerase-1 is a negative regulator of HIV-1 transcription through competitive binding to TAR RNA with Tat.positive transcription elongation factor b (p-TEFb) complex
    Marianne Parent
    Division of Health and Environmental Research, Laval University Medical Center, Ste Foy, Quebec G1V 4G2, Canada
    J Biol Chem 280:448-57. 2005
    ..Thus, these results suggest that PARP-1 acts as a negative regulator of HIV-1 transcription through competitive binding with Tat or the Tat.P-TEFb complex to TAR RNA...
  64. doi Cyclin-dependent kinase 7/9 inhibitor SNS-032 abrogates FIP1-like-1 platelet-derived growth factor receptor α and bcr-abl oncogene addiction in malignant hematologic cells
    Yongbin Wu
    Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat Sen University, 74 Zhongshan Road II, Guangzhou 510089, PR China
    Clin Cancer Res 18:1966-78. 2012
    ..of this study was to evaluate the strategy of shutting down the transcription and expression of FIP1-like-1 (FIP1L1)-PDGFRα and Bcr-Abl with SNS-032, an inhibitor of cyclin-dependent kinase 7 (CDK7) and CDK9 in phase I clinical trials.
  65. ncbi Phosphorylated positive transcription elongation factor b (P-TEFb) is tagged for inhibition through association with 7SK snRNA
    Ruichuan Chen
    Department of Molecular and Cell Biology, University of California, Berkeley, California 94720 3202, USA
    J Biol Chem 279:4153-60. 2004
    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...
  66. doi Promoter influences transcription elongation: TATA-box element mediates the assembly of processive transcription complexes responsive to cyclin-dependent kinase 9
    Immaculada Montanuy
    Department of Molecular Biology and Cell Biology, Instituto de Parasitologia y Biomedicina Lopez Neyra, Consejo Superior de Investigaciones Cientificas, 18100 Granada, Spain
    J Biol Chem 283:7368-78. 2008
    ..We determined that cyclin-dependent kinase 9 (CDK9), the kinase subunit of positive transcription elongation factor b (P-TEFb) complex, regulates transcriptional ..
  67. pmc CDK9 autophosphorylation regulates high-affinity binding of the human immunodeficiency virus type 1 tat-P-TEFb complex to TAR RNA
    M E Garber
    Regulatory Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    Mol Cell Biol 20:6958-69. 2000
    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-..
  68. pmc The mechanism of release of P-TEFb and HEXIM1 from the 7SK snRNP by viral and cellular activators includes a conformational change in 7SK
    Brian J Krueger
    Molecular and Cellular Biology Program, University of Iowa, Iowa City, Iowa, United States of America
    PLoS ONE 5:e12335. 2010
    ..Expression of HIV-1 Tat leads to release of P-TEFb and HEXIM1 from the 7SK snRNP in vivo, but the release mechanisms are unclear...
  69. pmc Cyclin K inhibits HIV-1 gene expression and replication by interfering with cyclin-dependent kinase 9 (CDK9)-cyclin T1 interaction in Nef-dependent manner
    Sohrab Zafar Khan
    National Centre for Cell Science, Ganeshkhind, Pune 411007, India
    J Biol Chem 286:22943-54. 2011
    ..The positive elongation factor b complex comprising cyclin-dependent kinase 9 (CDK9) and Cyclin T1 is a critical cellular complex required for viral gene expression and replication...
  70. pmc Regulation of human immunodeficiency virus type 1 gene expression by clade-specific Tat proteins
    Yan Desfosses
    McGill AIDS Center, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, 3755 Cote Ste Catherine, Montreal, Quebec, Canada H3T1E2
    J Virol 79:9180-91. 2005
    ..Swapping the activation domains of Tat B, C, and E identified the cyclin T1 association domain as a critical determinant of the transactivation efficiency and of Tat-defective HIV-1 provirus rescue...
  71. doi Induction of monocyte chemoattractant protein-1 (MCP-1/CCL2) gene expression by human immunodeficiency virus-1 Tat in human astrocytes is CDK9 dependent
    Abdelkader Khiati
    INSERM U802 and Université Paris Sud 11, Faculte de Medecine Paris Sud, Le Kremlin Bicetre, France
    J Neurovirol 16:150-67. 2010
    ..factor kappaB (NF-kappaB) classical pathway, but was significantly inhibited by specific cyclin-dependent kinase 9 (cdk9) inhibitors, such as a dominant-negative mutant or siRNA...
  72. ncbi Reciprocal modulation of transcriptional activities between HIV-1 Tat and MHC class II transactivator CIITA
    H Okamoto
    Department of Molecular Genetics, Nagoya City University Medical School, 1 Kawasumi, Mizuho cho, Mizuho ku, Nagoya, Aichi, 467 8601, Japan
    Biochem Biophys Res Commun 279:494-9. 2000
    ..These reciprocal actions between Tat and CIITA not only explains the functional impairment of APC in HIV-1 infection but also rationalizes the suppression of HIV-1 virus load by induction of CIITA such as IFN-gamma...
  73. pmc HIV-1 Tat assembles a multifunctional transcription elongation complex and stably associates with the 7SK snRNP
    Bijan Sobhian
    Laboratoire de Virologie Moleculaire, Institut de Genetique Humaine, CNRS UPR1142, Montpellier, France
    Mol Cell 38:439-51. 2010
    ..Importantly, Tatcom1 formation relies on P-TEFb while optimal CDK9 CTD-kinase activity is AF9 dependent. MLL-fusion partners and PAF1 are required for Tat transactivation...
  74. pmc Acetylation of cyclin T1 regulates the equilibrium between active and inactive P-TEFb in cells
    Sungyoo Cho
    Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94158, USA
    EMBO J 28:1407-17. 2009
    ..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...
  75. pmc The ubiquitin ligase Siah1 controls ELL2 stability and formation of super elongation complexes to modulate gene transcription
    Min Liu
    School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China
    Mol Cell 46:325-34. 2012
    ..Given its importance in formation of SECs, the Siah1 ubiquitination pathway provides a fresh avenue for developing strategies to control disease-related transcription...
  76. doi Functions of Tat: the versatile protein of human immunodeficiency virus type 1
    Bizhan Romani
    Division of Medical Virology, Department of Pathology, University of Stellenbosch, Tygerberg 7505, South Africa
    J Gen Virol 91:1-12. 2010
    ..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...
  77. pmc Regulation of P-TEFb elongation complex activity by CDK9 acetylation
    Junjiang Fu
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Mol Cell Biol 27:4641-51. 2007
    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...
  78. pmc A novel RNA polymerase II-containing complex potentiates Tat-enhanced HIV-1 transcription
    C A Parada
    Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10021, USA
    EMBO J 18:3688-701. 1999
    ..Our results indicate that Tat-SF is a Tat cofactor-containing RNA Pol II complex whose recruitment to the promoter provides elongation factors important for Tat-enhanced HIV-1 transcription following TAR RNA synthesis...
  79. ncbi Three RNA polymerase II carboxyl-terminal domain kinases display distinct substrate preferences
    Y Ramanathan
    Department of Biochemistry and Molecular Biology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA
    J Biol Chem 276:10913-20. 2001
    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...
  80. pmc HIV-1 tat transcriptional activity is regulated by acetylation
    R E Kiernan
    Laboratoire de Virologie Moléculaire et Transfert de Gène, Institut de Genetique Humaine, UPR1142 Montpellier, 34396, France
    EMBO J 18:6106-18. 1999
    ..Mechanistically, acetylation at Lys28 by PCAF enhanced Tat binding to the Tat-associated kinase, CDK9/P-TEFb, while acetylation by p300 at Lys50 of Tat promoted the dissociation of Tat from TAR RNA that occurs during ..
  81. pmc Transcription elongation factor P-TEFb mediates Tat activation of HIV-1 transcription at multiple stages
    Q Zhou
    Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA
    EMBO J 17:3681-91. 1998
    ..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 ..
  82. ncbi HEXIM2, a HEXIM1-related protein, regulates positive transcription elongation factor b through association with 7SK
    Sarah A Byers
    Molecular Biology Program and Department of Biochemistry, University of Iowa, Iowa City, Iowa 52242, USA
    J Biol Chem 280:16360-7. 2005
    ..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...
  83. pmc Phosphorylation of the RNA polymerase II carboxyl-terminal domain by CDK9 is directly responsible for human immunodeficiency virus type 1 Tat-activated transcriptional elongation
    Young Kyeung Kim
    Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom
    Mol Cell Biol 22:4622-37. 2002
    Stimulation of transcriptional elongation by the human immunodeficiency virus type 1 Tat protein is mediated by CDK9, a kinase that phosphorylates the RNA polymerase II carboxyl-terminal domain (CTD)...
  84. ncbi The regulation of HIV-1 transcription: molecular targets for chemotherapeutic intervention
    Miguel Stevens
    Rega Institute for Medical Research, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    Med Res Rev 26:595-625. 2006
    ..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...
  85. pmc Induction of TAK (cyclin T1/P-TEFb) in purified resting CD4(+) T lymphocytes by combination of cytokines
    R Ghose
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Virol 75:11336-43. 2001
    ..Tat function is mediated by a cellular protein kinase known as TAK (cyclin T1/P-TEFb) that is composed of Cdk9 and cyclin T1...
  86. ncbi NF-kappaB binds P-TEFb to stimulate transcriptional elongation by RNA polymerase II
    M Barboric
    Howard Hughes Medical Institute Departments of Medicine, Microbiology, and Immunology University of California at San Francisco 94143, USA
    Mol Cell 8:327-37. 2001
    ..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...
  87. ncbi Regulation of TAK/P-TEFb in CD4+ T lymphocytes and macrophages
    Andrew P Rice
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
    Curr HIV Res 1:395-404. 2003
    ..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...
  88. pmc Human Polymerase-Associated Factor complex (PAFc) connects the Super Elongation Complex (SEC) to RNA polymerase II on chromatin
    Nanhai He
    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 108:E636-45. 2011
    ..This finding explains the YEATS domain's dispensability for leukemogenesis when ENL/AF9 is translocated to MLL, whose interactions with PAFc and DNA likely substitute for the PAFc/chromatin-targeting function of the YEATS domain...
  89. pmc A human splicing factor, SKIP, associates with P-TEFb and enhances transcription elongation by HIV-1 Tat
    Vanessa Brès
    Regulatory Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    Genes Dev 19:1211-26. 2005
    HIV-1 Tat binds human CyclinT1 and recruits the CDK9/P-TEFb complex to the viral TAR RNA in a step that links RNA polymerase II (RNAPII) C-terminal domain (CTD) Ser 2 phosphorylation with transcription elongation...
  90. ncbi The Cdk9 and cyclin T subunits of TAK/P-TEFb localize to splicing factor-rich nuclear speckle regions
    C H Herrmann
    Dept of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
    J Cell Sci 114:1491-503. 2001
    ..TAK/P-TEFb is composed of Cdk9 and cyclin T and serves as the cellular cofactor for the human immunodeficiency virus transactivator Tat protein...
  91. pmc Control of HIV latency by epigenetic and non-epigenetic mechanisms
    Uri Mbonye
    Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Curr HIV Res 9:554-67. 2011
    ....
  92. ncbi Positive transcription elongation factor B phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase
    J B Kim
    Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Biol Chem 276:12317-23. 2001
    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...
  93. ncbi c-Myc recruits P-TEFb for transcription, cellular proliferation and apoptosis
    Satoshi Kanazawa
    Departments of Medicine, Microbiology and Immunology, Rosalind Russell Medical Research Center, University of California, San Francisco, CA 94143 0703, USA
    Oncogene 22:5707-11. 2003
    ..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 ..
  94. pmc Sustained induction of NF-kappa B is required for efficient expression of latent human immunodeficiency virus type 1
    Samuel A Williams
    Gladstone Institute of Virology and Immunology, University of California San Francisco, 1650 Owens Street, San Francisco, CA 94158, USA
    J Virol 81:6043-56. 2007
    ..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, ..
  95. pmc Cyclin T1-dependent genes in activated CD4 T and macrophage cell lines appear enriched in HIV-1 co-factors
    Wendong Yu
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America
    PLoS ONE 3:e3146. 2008
    ..The presence of CTDGs in the protein space that was available for HIV-1 to sample during its evolution and acquisition of Tat function may provide an explanation for why CTDGs are enriched in viral co-factors...
  96. pmc Optimized chimeras between kinase-inactive mutant Cdk9 and truncated cyclin T1 proteins efficiently inhibit Tat transactivation and human immunodeficiency virus gene expression
    Koh Fujinaga
    Department of Medicine, University of California at San Francisco, San Francisco, California 94143 0703, USA
    J Virol 76:10873-81. 2002
    ..and thus HIV replication, we constructed mutant hCycT1 proteins that are defective in binding its kinase partner, Cdk9, or TAR...
  97. pmc CDK9 is constitutively expressed throughout the cell cycle, and its steady-state expression is independent of SKP2
    Judit Garriga
    Fels Institute for Cancer Research and Molecular Biology, Department of Biochemistry, Temple University School of Medicine, 3307 North Broad Street, Philadelphia, PA 19140, USA
    Mol Cell Biol 23:5165-73. 2003
    b>CDK9 is a CDC2-related kinase and the catalytic subunit of the positive-transcription elongation factor b and the Tat-activating kinase...
  98. pmc Cdk9 T-loop phosphorylation is regulated by the calcium signaling pathway
    Rajesh Ramakrishnan
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Cell Physiol 227:609-17. 2012
    ..The core P-TEFb complex is composed of Cdk9 and Cyclin T and is essential for the expression of most protein coding genes...
  99. pmc Manipulation of P-TEFb control machinery by HIV: recruitment of P-TEFb from the large form by Tat and binding of HEXIM1 to TAR
    Stanley C Sedore
    Department of Biochemistry, University of Iowa, Iowa City, IA, USA
    Nucleic Acids Res 35:4347-58. 2007
    ..This suggests that in the absence of Tat, HEXIM1 may bind to TAR and repress transcription elongation of the HIV LTR...
  100. ncbi Role of the HIV-1 positive elongation factor P-TEFb and inhibitors thereof
    Yan Wang
    Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, No 44 Wenhuaxi Road, Jinan 250012, China
    Mini Rev Med Chem 9:379-85. 2009
    ..The positive elongation factor P-TEFb, a heterodimer containing a catalytic subunit (CDK9) and unique regulatory cyclins (CycT1), is required for HIV-1 Tat transcriptional activation...
  101. ncbi Upregulation of cyclin T1/CDK9 complexes during T cell activation
    J Garriga
    Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA
    Oncogene 17:3093-102. 1998
    Cyclin T1 has been identified recently as a regulatory subunit of CDK9 and as a component of the transcription elongation factor P-TEFb...

Research Grants64

  1. Tat and CDK9 on gene expression alterations coupled to HIV-1 Associated Dementia
    Xavier Grana; Fiscal Year: 2010
    ..with a cellular kinase composed of a regulatory subunit designated cyclin T1 and a catalytic subunit named CDK9. This host complex is recruited by Tat to TAR, an RNA element in the nascent HIV-1 transcript, where CDK9 is ..
  2. Tat Transactivation
    BORIS MATIJA PETERLIN; Fiscal Year: 2013
    ..Importantly, CycK does not bind Cdk9, which together with CycT1 or CycT2 forms P-TEFb...
  3. Structure and Function of Ribonucleoprotein Complexes Modulating HIV Replication
    TARIQ RANA; Fiscal Year: 2009
    ..Tat interacts with cyclinT1 (CycT1), a regulatory partner of CDK9 in the positive transcription elongation factor b (P-TEFb) complex, and binds cooperatively with CycT1 to TAR RNA...
  4. Structure and Function of Ribonucleoprotein Complexes Modulating HIV Replication
    Tariq M Rana; Fiscal Year: 2013
    ..Tat interacts with cyclinT1 (CycT1), a regulatory partner of CDK9 in the positive transcription elongation factor b (P-TEFb) complex, and binds cooperatively with CycT1 to TAR RNA...
  5. P-TEFb and HIV Latency
    Andrew P Rice; Fiscal Year: 2013
    ..factor involved in the viral Tat protein's function Core P-TEFb is composed of Cyclin T1 (CCNT1) and CDK9. Recent results in a primary CD4+ T lymphocyte system of HIV-1 latency have shown that CCNT1 protein and CDK9 T-..
  6. Regulation of Transcriptional Elongation by HIV-1 TAT
    Qiang Zhou; Fiscal Year: 2013
    Project Summary/Abstract The general transcription factor P-TEFb, consisting of Cdk9 and cyclin T, strongly stimulates RNA polymerase II elongation. It is also a host cell cofactor for Tat activation of HIV-1 transcription...
  7. CYCLIN T AND HIV1 TAT TRANSACTIVATION
    Katherine A Jones; Fiscal Year: 2013
    Project Summary The HIV-1 Tat transactivator interacts with P-TEFb (Cyclin T1:CDK9) and the AFF4:AFF1:AF9:ENL:ELL2 complex to stimulate elongation at the HIV-1 promoter...
  8. Cyclin-Dependent Kinase Inhibition During S Phase
    Geoffrey I Shapiro; Fiscal Year: 2013
    ..family members, the second specific aim will focus on cells in which there is combined depletion of cdk2, cdk1 and cdk9. Depletion or inhibition of this subset of cdks induces apoptosis...
  9. Mechanisms in transcriptional regulation during cardiac hypertrophy
    Maha Abdellatif; Fiscal Year: 2013
    ..two major components of basic transcription, general transcription factor 2B (TFIIB) and cyclin-dependent kinase 9 (Cdk9), which are the key regulators of pol II recruitment and elongation, respectively...
  10. Transcriptional regulation of H. pylori-mediated gastric inflammation and cancer
    Lin Feng Chen; Fiscal Year: 2013
    ..the general transcriptional elongation factor P-TEFb (the positive transcription elongation factor b), comprised of CDK9 and Cyclin T1, is essential for the expression of NF-?B-dependent inflammatory genes...
  11. Mechanism of HIV-1 Tat Function
    Andrew Rice; Fiscal Year: 2009
    ..Tat function is mediated by a cellular protein kinase termed P-TEFb that is composed of Cyclin T1 and Cdk9. Tat binds directly to Cyclin T1, and Tat/Cyclin T1/Cdk9 then associate with the viral TAR RNA structure that forms ..
  12. Effect of chromatin remodelers/modifiers on HIV-1 Tat activated transcription
    Fatah Kashanchi; Fiscal Year: 2010
    ..transcriptional level in HIV-1 infected cells by binding the trans-activation response region (TAR) and recruiting cdk9/cyclin T1, p300/CBP, SWI/SNF, and RNA Polymerase II...
  13. Novel CTD inhibitors with synthetic lethality to oncogenic Ras for cancer therapy
    Bingliang Fang; Fiscal Year: 2013
    ..of PKCiota and splicing factors in megaspliceosomes and to disruption of the interaction between PKCiota and CDK9/cyclin T1 complex, which phosphorylates the CTD...
  14. Identification of novel co-factors for HIV Tat and Rev as therapeutic targets
    Andrew P Rice; Fiscal Year: 2013
    ..P-TEFb is composed of Cyclin T1 (CCNT1) as a regulatory subunit and CDK9 as the catalytic subunit;Tat binds directly to CCNT1...
  15. Novel Early Intervention to Prevent Post-Traumatic Osteoarthritis
    Dominik R Haudenschild; Fiscal Year: 2013
    ..the transcription elongation step, with the rate-limiting step being the recruitment of cyclin-dependent kinase-9 (cdk9) to the transcription complex by NF?B...
  16. Effect of Iron Chelators on HIV-1 transcription
    ZUFAN KEREGO DEBEBE; Fiscal Year: 2011
    ..aim will study if iron chelators inhibit expression and cellular activities of the cyclin dependent kinase 9 (CDK9) and CDK2...
  17. HIV-1 Inhibition using Tat Peptide Derivatives
    Fatah Kashanchi; Fiscal Year: 2013
    ..the original Tat 15 aa peptide inhibitor to 5 aa and have found the new peptide to be able to bind to cdk2, and cdk9 tightly and inhibit their kinase activity both in vitro and in vivo...
  18. Phosphorylation of CDK9 by CDK2 in HIV-1 replication
    Denitra Breuer; Fiscal Year: 2011
    ..Our preliminary results indicate that CDK2 might phosphorylate CDK9 and affect the kinase activity of CDK9/cyclin T1 complex in the cells that have a reduced CDk2 expression...
  19. Cyclin-dependent Kinases and Cardiac Growth
    Michael Schneider; Fiscal Year: 2007
    ..basal transcription factors, TFIIH (cyclin HCdk7) and positive transcription elongation factor b (P-TEFb, cyclin T-Cdk9)...
  20. Phosphorylation and Functions of the RNA Polymerase CTD
    Arno L Greenleaf; Fiscal Year: 2013
    ..the CTD determines which proteins bind to it, we are characterizing the activities and chromosomal distribution of Ctk1-kinase, the principal elongation-phase CTD kinase in yeast...
  21. IMPACT OF TUBERCULOSIS ON HIV DISEASE
    Zahra Toossi; Fiscal Year: 2009
    ..Also, the CDK9 inhibitor Indirubicin Monoxime (IM), blocks transcriptional elongation of HIV by P-TEFb in both CD4 T-cells and ..
  22. Proteins Mediating Interaction of HIV-1 and JCV in CNS
    Edward M Johnson; Fiscal Year: 2011
    ..how the Smad nuclear effectors of TGF-31 interact with Tat and its cellular partner proteins Pura and Cyclin T1/ Cdk9 at JCV and PCNA promoter sequences...
  23. IMPACT OF TUBERCULOSIS ON HIV DISEASE
    ZAHRA TOOSSI TOOSSI; Fiscal Year: 2013
    ..These include;1. Derivatives of erythromycin, some of which may be useful in MDR TB, 2. an inhibitor of CDK9 (of P-TEFb), Indirubicin Monoxime, and 3...
  24. Role of CDK9 in the Replication Stress Response
    David Yu; Fiscal Year: 2013
    ..in human cells to identify 14 high-confidence RSR genes, including the novel RSR gene, cyclin-dependent kinase 9 (CDK9)...
  25. Transcriptional Deregulation by MLL Fusion Proteins
    Jay L Hess; Fiscal Year: 2011
    ..called MPAC (MLL Partner Activation Complex) that includes Dot1, a histone H3 lysine 79 methyltransferase, and CDK9/CyclinT1/T2, which phosphorylates the C terminal domain of RNA polymerase II...
  26. REGULATION OF THE TAT ASSOCIATED KINASE, TAK
    CHRISTINE HERRMANN; Fiscal Year: 2002
    ..A cellular protein kinase, TAK, has been identified in their laboratory that specifically associates with the activation domain of Tat and is ..
  27. Regulation of HIV transcription by Tat and P-TEPb
    TSAFI PE ERY; Fiscal Year: 2004
    ..P-TEFb (cyclin T1/CDK9) is a cellular transcription elongation factor that cooperates with the viral protein Tal to attain processive ..
  28. REGULATION OF HIV1 GENE EXPRESSION BY TAT AND TAR
    Michael Mathews; Fiscal Year: 2001
    ..TAK and P-TEFb share at least one subunit, the CDC2-related kinase PITALRE. The major objectives of this grant are to evaluate the hypothesis that Tat acts via TAK/P-TEFb, and to extend it ..
  29. Role of Androgen Receptor Phosphorylation in Prostate Cancer
    Daniel G Gioeli; Fiscal Year: 2012
    ..The following specific aims are proposed: 1) Specific Aim 1: Examine the effect of AR Ser81 phosphorylation by CDK9 on AR transcriptional activity;2) Specific Aim 2: Determine the effect of the cell cycle on AR phosphorylation and ..
  30. Regulation of Tak/P-TEFb
    Andrew Rice; Fiscal Year: 2003
    ..Tat function is mediated by a cellular protein kinase complex termed TAK/P-TEFb. This kinase is composed of Cdk9 as the catalytic subunit, and cyclin T1 as a regulatory subunit that makes direct protein-protein contact with Tat...
  31. Hexim-1, a novel regulator of prostate cancer progression
    MANYA DHAR MASCARENO; Fiscal Year: 2012
    ..To this end, we have identified Hexim-1, a strong Cdk9 inhibitor, as a novel player in the progression of prostate cancer...
  32. Mechanisms of HIV-1 latency in CD4+ T lymphocytes
    Andrew Rice; Fiscal Year: 2007
    ..TAK/P-TEFb is a cellular protein kinase composed of CDK9 as the catalytic subunit and cyclin T1 as a regulatory subunit...
  33. Transcriptional regulation by protein kinase CDC2L5
    JASPER YIK; Fiscal Year: 2006
    ..by applicant): The CDC2-related protein kinase, CDC2L5, shares extensive sequence homology and characteristics with CDK9, the kinase subunit of the general transcription elongation factor P-TEFb, which is also important for the ..
  34. Effect of Bacterial Tolerance on TLR4 Signal Transduction
    Andrei E Medvedev; Fiscal Year: 2013
    ..LPS- induced c-Src and Lyn phosphorylation and Lyn-TLR4 interactions;inhibited activation of kinases IRAK4 and TAK-1;impaired K63-linked polyubiquitination of IRAK1 and TRAF-6;suppressed interactions of ubiquitinated IRAK1 with ..
  35. MOLECULAR MECHANISM OF TAT INDUCED ANGIOGENESIS
    Cindy Morris; Fiscal Year: 2002
    ..region domains of Tat, plays a role during angiogenesis, (2) an endothelial cell-derived cyclin-dependent kinase, TAK/pTEF-b, activity that is essential for Tat transactivation, is induced through activation of primary human vascular ..
  36. The role of Burkholderia in giant cell arteritis
    Curry Koening; Fiscal Year: 2013
    ..GCA also has similar histological features similar to Takayasu's arteritis (TAK), a granulomatous arteritis of large and medium-sized blood vessels that affects young women...
  37. Mechanisms of SIRT2 Function in the Replication Stress Response
    David Yu; Fiscal Year: 2013
    ..Recent data from the lab show that SIRT2 deacetylates CDK9 at a conserved lysine residue to promote recovery from replication arrest...
  38. Mass spectrometry of proteome, phosphoproteome and phosphatase-targeted drug desi
    Yuri Obukhov; Fiscal Year: 2012
    ..Specifically, we will analyze PP1-associated protein complexes that target PP1 to CDK9, Sp1 or RNAPII and other yet unknown proteins...
  39. Function and localization of HIV cofactor TAK/P-TEFb
    CHRISTINE HERRMANN; Fiscal Year: 2005
    ..Transactivation by Tat requires the cellular cofactor, TAWP-TEFb, which is composed of the catalytic subunit Cdk9 and regulatory subunit cyclin T1...
  40. Molecular Mechanisms of Gene Silencing by RNAi
    Richard W Carthew; Fiscal Year: 2013
    ..Our aims are to: 1) determine how the nuclear Cdk9 kinase recruits a protein complex to co-transcriptionally cleave RNA transcripts into miRNAs, 2) determine how ..
  41. REGULATION OF MONOCYTE RECRUITMENT INTO THE ISCHEMIC MYOCARDIUM BY THE ACE2 AXIS
    Slava Epelman; Fiscal Year: 2013
    ..The PI will tak advantage of this mentorship and the enormous basic science and clinical resources available at Washington ..
  42. Mechanisms regulating HIV-1 gene expression
    Udit Verma; Fiscal Year: 2005
    ..is mediated by its binding to TAR RNA in conjunction to the pTEF-b kinase complex comprised of cyclin Ti and CDK9 to increase the activity of the elongation factors SPT4/SPT5...
  43. Role of adipocytes in local and systemic inflammation
    Chantal A Rivera; Fiscal Year: 2010
    ..b>Tak Yee Aw and Dr. Mathew Grisham...
  44. A RasGAP-microRNA connection in cardiac hypertrophy
    Maha Abdellatif; Fiscal Year: 2012
    ..Subsequently, down-regulation of miR- 1 results in upregulation of its targets that include: RasGAP, Cdk9, fibronectin, endothelin, and insulin-like growth factor, among others...
  45. Exploring the Role of TAK1 in Neuronal Polarization
    MEGHAN LYNN MORGAN-SMITH; Fiscal Year: 2011
    ..I have obtained preliminary results suggesting that the serine/threonine kinase, TGF-P activated kinase 1 (TAK 1) phosphorylates S431 on LKB1 and my project is aimed at determining the biological relevance of TAK1 in the ..
  46. c-Jun N-terminal kinase and joint destruction in RA
    Gary S Firestein; Fiscal Year: 2012
    ..Third, we will examine how Gadd45ss and upstream kinases like TAK 1 regulate MKK4 and MKK7 activation in FLS...
  47. Tak1, a novel prostate cancer tumor suppressor
    Scott D Cramer; Fiscal Year: 2013
    ..role of Tak1 as a key integrator of multiple signals from the microenvironment, we propose the hypothesis that Tak 1 is a tumor suppresser for prostate cancer and that Tak1 functions to regulate growth and or differentiation of ..
  48. CONCURRENT PILOT STUDIES IN GIANT CELL ARTERITIS AND TAKAYASUS ARTERITIS TO EXAM
    Avery Gottfried; Fiscal Year: 2011
    ..the medication abatacept is safe in the treatment of giant cell arteritis (GCA) and Takayasu's arteritis (TAK) and whether there is evidence of effectiveness to support pursuing this medication in larger scale studies...
  49. Amantadine + rTMS as a Neurotherapeutic for Disordered Consciousness after TBI
    Theresa Louise Bender Pape; Fiscal Year: 2013
    ..ac- tivity resulting in improved function for persons incurring severe TBI and this R21 addresses this need by tak-ing the first step toward developing a robust and safe treatment...
  50. A Tool for Modeling the Structure-Activity of Chemokine Receptors and Other GPCRs
    BENJAMIN DORANZ; Fiscal Year: 2009
    ..with a chemokine (RANTES), two monoclonal antibodies (2D7 and 45523), HIV-1 Env (JRFL), and a small- molecule drug (TAK-779). Our results were validated against and agree with published results...
  51. HIV-1 Resistance to Chemokine Receptor Antagonists
    Daniel R Kuritzkes; Fiscal Year: 2013
    ..over a range of CCR5 and CD4 levels using Affinofile cells in the presence of various concentrations of VCV or TAK-779. 2)To determine affinity of CCR5 antagonist-resistant HIV-1 envelopes for CD4 and CCR5...
  52. DOPAMINE & ENKEPHALIN/TACHYKININ IN BASAL GANGLION
    SUBBIAH SIVAM; Fiscal Year: 1992
    ..g. Met5-enkephalin) and tachykinin (TAK, e.g. substance P) containing peptidergic neurons of the basal ganglia...
  53. Identification of Small Pharmacologic Inhibitors of HIV-1 Replication
    Xavier Grana; Fiscal Year: 2007
    ..One such "indirect target" is the cyclin T1/CDK9 complex, which is essential for HIV Tat-mediated transactivation...
  54. Evaluation of Loop-mediated isothermal amplification for rapid malaria diagnosis
    SUREEMAS BUATES; Fiscal Year: 2009
    ..Optimization of LAMP will be done at Mahidol laboratory and then at Maesod malaria clinic in Tak province, Thailand...
  55. Protein inhibitor of Raf-1 kinase
    Kam Yeung; Fiscal Year: 2005
    ..NF-kB activation, and I have shown that RKIP physically interacts with two components of the NF-kB cascade, NIK and TAK 1. I will employ a combination of genetic and biochemical methods to study the effects of RKIP on NF-kB signaling...
  56. Interaction between HIV-1 and cell cycle proteins
    Antonio Giordano; Fiscal Year: 2003
    ..Among the latter, Cdk9 (PITALRE), identified and cloned in our laboratory, is the most likely candidate to be involved in the development of AIDS-..
  57. T-TYPE CYCLIN/CDK9 COMPLEXES IN T CELL ACTIVATION
    Xavier Grana; Fiscal Year: 2004
    ..aims are as follows: First, To elucidate the mechanisms leading to upregulation of individual T-type cyclin/CDK9 complexes during both T cell activation and differentiation of myeloid cells along the monocyte/macrophage lineage...
  58. Molecular mechanisms of cellular gene expression reprogramming by HIV Tat protein
    Anna Aldovini; Fiscal Year: 2009
    ..with TAR, a RNA sequence present at the beginning of the HIV viral transcripts, and with the host cell factors CDK9 and cyclin T1...
  59. Targeting Human Cyclin T1 to Inhibit HIV-1 Replication
    Wayne Marasco; Fiscal Year: 2004
    HIV-1 Tat protein is absolutely required for viral replication. Tat functions in concert with the cellular kinase cdk9 and human cyclinT1 (hCyclinT1) as a promoter-specific transcription elongation factor through binding to TAR in the 5'-..
  60. REGULATION OF CYTOKINES BY HIV1 TAT IN CENTRAL NERVOUS S
    Shohreh Amini; Fiscal Year: 2004
    ..have shown that LTR activation by Tat may require several cellular proteins including cyclin T1 and its partner cdk9, which associate with Tat and TAR and are positioned near the transcription start site...
  61. REGULATION OF HIV-1 GENE TRANSCRIPTION IN CNS
    Bassel Sawaya; Fiscal Year: 2004
    ..cooperative interaction of this viral protein with several cellular factors including cyclin T and its partner, cdk9, and the LTR sequence called TAR, which is positioned between +19 to +43 with respect to the transcription start ..
  62. MEETING ON MOLECULAR BASIS OF TUMOR IMMUNOLOGY
    Ellen Vitetta; Fiscal Year: 1990
    ..The Organizing Committee for this conference consists of Drs. Tak W. Mak, Chairperson; Lloyd J. Old; and Ellen S. Vitetta, Principal Investigator...
  63. FUNCTIONS FOR HERPES SIMPLEX VIRUS ICP22 AND US1.5
    Bernard Roizman; Fiscal Year: 2009
    ..ii) ICP22 and UL13 mediate an aberrant phosphorylation of RNA POL II. We found that ICP22 interacts with cdk9, a T1 cyclin-dependent kinase involved in transcriptional activation...
  64. INTRACEULLULAR ANTI-TAT ANTIBODIES FOR AIDS GENE THERAPY
    Wayne Marasco; Fiscal Year: 2002
    ..anti-hCycT1 intrabodies that block binding of hCycT1 to Tat protein and TAR RNA but do not disrupt hCycT1-cdk9 interactions, since blocking the hCycT1-cdk9 protein:protein interaction could disrupt the normal functioning of ..