cdk9

Summary

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

Top Publications

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. ncbi Cyclin T1 domains involved in complex formation with Tat and TAR RNA are critical for tat-activation
    D Ivanov
    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 288:41-56. 1999
  7. 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
  8. 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
  9. 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
  10. 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

Research Grants

  1. Tat and CDK9 on gene expression alterations coupled to HIV-1 Associated Dementia
    Xavier Grana; Fiscal Year: 2010
  2. BORIS MATIJA PETERLIN; Fiscal Year: 2015
  3. Structure and Function of Ribonucleoprotein Complexes Modulating HIV Replication
    TARIQ RANA; Fiscal Year: 2009
  4. Structure and Function of Ribonucleoprotein Complexes Modulating HIV Replication
    Tariq M Rana; Fiscal Year: 2013
  5. Qiang Zhou; Fiscal Year: 2016
  6. P-TEFb and HIV Latency
    Andrew P Rice; Fiscal Year: 2013
  7. Maha Abdellatif; Fiscal Year: 2016
  8. Geoffrey I Shapiro; Fiscal Year: 2014
  9. Mechanism of HIV-1 Tat Function
    Andrew Rice; Fiscal Year: 2009
  10. Lin Feng Chen; Fiscal Year: 2015

Detail Information

Publications281 found, 100 shown here

  1. 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--..
  2. 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...
  3. 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...
  4. 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 ..
  5. 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...
  6. ncbi Cyclin T1 domains involved in complex formation with Tat and TAR RNA are critical for tat-activation
    D Ivanov
    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 288:41-56. 1999
    ..Recently, it has been demonstrated that the cellular kinase CDK9 and its binding partner cyclin T1 are involved in regulating transcriptional elongation and tat-activation...
  7. 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)...
  8. 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...
  9. 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...
  10. 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...
  11. 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...
  12. 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...
  13. 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...
  14. 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...
  15. 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/..
  16. 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...
  17. 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...
  18. 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
    ....
  19. 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)...
  20. 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
    ....
  21. 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)...
  22. 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...
  23. 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...
  24. 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 ..
  25. 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
    ....
  26. 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.
  27. 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...
  28. 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...
  29. 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...
  30. 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...
  31. 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...
  32. 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 ..
  33. 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...
  34. 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)...
  35. 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 ..
  36. 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 ..
  37. 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...
  38. pmc The ability of positive transcription elongation factor B to transactivate human immunodeficiency virus transcription depends on a functional kinase domain, cyclin T1, and Tat
    K Fujinaga
    Departments of Medicine, Microbiology, and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California 94143 0703, USA
    J Virol 72:7154-9. 1998
    ..Two cyclin-dependent serine/threonine kinases, CDK7 and CDK9, which phosphorylate the C-terminal domain of RNA polymerase II, have been implicated in Tat transactivation in ..
  39. 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...
  40. 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)...
  41. ncbi Cyclin K functions as a CDK9 regulatory subunit and participates in RNA polymerase II transcription
    T J Fu
    Department of Biology, Tularik Inc, South San Francisco, California 92080, USA
    J Biol Chem 274:34527-30. 1999
    ..The P-TEFb complex isolated from mammalian cells contains a catalytic subunit (CDK9), a cyclin subunit (cyclin T1 or cyclin T2), and additional, yet unidentified, polypeptides of unknown function...
  42. 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...
  43. 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...
  44. 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...
  45. 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...
  46. 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...
  47. 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, ..
  48. 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...
  49. 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
    ....
  50. pmc Domains in the SPT5 protein that modulate its transcriptional regulatory properties
    D Ivanov
    Division of Hematology Oncology, Department of Medicine, Harold Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75235 8594, USA
    Mol Cell Biol 20:2970-83. 2000
    ..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...
  51. pmc Tat activates human immunodeficiency virus type 1 transcriptional elongation independent of TFIIH kinase
    D Chen
    Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA
    Mol Cell Biol 19:2863-71. 1999
    ..transcriptional elongation by recruitment of the human transcription elongation factor P-TEFb, consisting of Cdk9 and cyclin T1, to the HIV-1 promoter via cooperative binding to the nascent HIV-1 transactivation response RNA ..
  52. pmc Human and rodent transcription elongation factor P-TEFb: interactions with human immunodeficiency virus type 1 tat and carboxy-terminal domain substrate
    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 Virol 73:5448-58. 1999
    ..transcriptional regulator Tat increases the efficiency of elongation, and complexes containing the cellular kinase CDK9 have been implicated in this process...
  53. pmc Host-cell positive transcription elongation factor b kinase activity is essential and limiting for HIV type 1 replication
    O Flores
    Department of Biology, Tularik, Inc, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 96:7208-13. 1999
    ..Selective inhibition of the P-TEFb kinase may therefore provide a novel approach for developing chemotherapeutic agents against HIV-1...
  54. pmc 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
    P D Bieniasz
    Howard Hughes Medical Institute and Department of Genetics, Box 3025, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 96:7791-6. 1999
    ..Activation by artificially recruited CycT1 depended on the ability to bind the CDK9 component of P-TEFb...
  55. ncbi HIV-1 TAR RNA enhances the interaction between Tat and cyclin T1
    J Zhang
    Department of Pharmacology, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    J Biol Chem 275:34314-9. 2000
    ..We conclude that TAR RNA nucleates the formation of the Tat.P-TEFb complex through an induced fit mechanism...
  56. ncbi Direct coupling of transcription and mRNA processing through the thermogenic coactivator PGC-1
    M Monsalve
    Dana Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 6:307-16. 2000
    ..PGC-1 can alter the processing of an mRNA, but only when it is loaded onto the promoter of the gene. These data demonstrate the coordinated regulation of RNA transcription and processing through PGC-1...
  57. ncbi Nuclear receptor coactivator p160 proteins enhance the HIV-1 long terminal repeat promoter by bridging promoter-bound factors and the Tat-P-TEFb complex
    Tomoshige Kino
    Pediatric and Reproductive Endocrinology Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 277:2396-405. 2002
    ..the N-terminal region of Tat and to the host cell protein cyclin T1, respectively, which is normally complexed with CDK9 as P-TEFb...
  58. pmc Spt5 cooperates with human immunodeficiency virus type 1 Tat by preventing premature RNA release at terminator sequences
    Cyril F Bourgeois
    MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, England
    Mol Cell Biol 22:1079-93. 2002
    ..transcription elongation by stimulating the Tat-activated kinase (TAK/p-TEFb), a protein kinase composed of CDK9 and its cyclin partner, cyclin T1...
  59. pmc Dynamics of human immunodeficiency virus transcription: P-TEFb phosphorylates RD and dissociates negative effectors from the transactivation response element
    Koh Fujinaga
    Department of Medicine, Rosalind Russell Medical Research Center, University of California at San Francisco, 3rd and Parnassus Avenue, San Francisco, CA 94143 0703, USA
    Mol Cell Biol 24:787-95. 2004
    ..b>Cdk9 in P-TEFb also phosphorylates RD at sites next to its RNA recognition motif...
  60. pmc Inhibition of human immunodeficiency virus type 1 replication by RNA interference directed against human transcription elongation factor P-TEFb (CDK9/CyclinT1)
    Ya Lin Chiu
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    J Virol 78:2517-29. 2004
    The human positive transcription elongation factor P-TEFb is composed of two subunits, cyclin T1 (hCycT1) and CDK9, and is involved in transcriptional regulation of cellular genes as well as human immunodeficiency virus type 1 (HIV-1) ..
  61. ncbi Multiple effects of HIV-1 trans-activator protein on the pathogenesis of HIV-1 infection
    M C D G Huigen
    Eijkman Winkler Center for Microbiology, Infectious Disease and Inflammation, Utrecht, The Netherlands
    Eur J Clin Invest 34:57-66. 2004
    ..These capacities together accelerate the progression towards AIDS and make Tat an interesting candidate as a constituent of an anti-AIDS vaccine...
  62. ncbi A review of HIV-1 Tat protein biological effects
    A Pugliese
    Department of Medical and Surgical Sciences, Section of Clinical Microbiology of Turin University, Amedeo di Savoia Hospital, Italy
    Cell Biochem Funct 23:223-7. 2005
    ..The effective role of HIV-1 Tat protein in promoting viral replication and its high immunogenicity suggest useful employment of this protein for therapeutic or preventive vaccine preparations...
  63. pmc Coordination of transcription factor phosphorylation and histone methylation by the P-TEFb kinase during human immunodeficiency virus type 1 transcription
    Meisheng Zhou
    Department of Biochemistry and Molecular Biology, The George Washington University School of Medicine, Washington, DC 20037, USA
    J Virol 78:13522-33. 2004
    ..Here we examine the role of the Tat/TAR-specified cyclin-dependent kinase 9 (CDK9) kinase activity in regulation of HIV-1 transcription elongation and histone methylation...
  64. pmc The carboxyl-terminal domain of RNA polymerase II is phosphorylated by a complex containing cdk9 and infected-cell protein 22 of herpes simplex virus 1
    Lizette O Durand
    The Marjorie B Kovler Viral Oncology Laboratories, The University of Chicago, 910 East 58th Street, Chicago, IL 60637, USA
    J Virol 79:6757-62. 2005
    ..Here we report another function of ICP22. Thus, ICP22 physically interacts with cdk9, a constitutively active cyclin-dependent kinase involved in transcriptional regulation...
  65. ncbi HIV-1 tat protein and cell proliferation and survival: a brief review
    Davide Gibellini
    Department of Clinical and Experimental Medicine, Microbiology Section, University of Bologna, Italy
    New Microbiol 28:95-109. 2005
    ..This review focuses on some aspects of Tat biological activity with particular regard to effects of Tat on cell proliferation and survival regulation...
  66. pmc Requirement for SWI/SNF chromatin-remodeling complex in Tat-mediated activation of the HIV-1 promoter
    Céline Treand
    Institut Cochin, Département de Génétique et Développement, Paris, France
    EMBO J 25:1690-9. 2006
    ..These data show the requirement of Tat-mediated recruitment of SWI/SNF chromatin-remodeling complex to HIV-1 promoter in the activation of the LTR...
  67. pmc Modulation of a P-TEFb functional equilibrium for the global control of cell growth and differentiation
    Nanhai He
    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    Mol Cell Biol 26:7068-76. 2006
    ..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...
  68. ncbi C/EBPbeta regulates human immunodeficiency virus 1 gene expression through its association with cdk9
    Giuseppe Mameli
    Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, 1900 N 12th Street 015 96, Philadelphia, PA 19122, USA
    J Gen Virol 88:631-40. 2007
    ..The HIV-1 Tat protein recruits the human positive transcription elongation factor P-TEFb, consisting of cdk9 and cyclin T1, to the HIV-1 transactivation response (TAR) region...
  69. 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...
  70. pmc 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
    X Yang
    Division of Molecular Virology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 94:12331-6. 1997
    ..Virol. 69, 1612-1620]. We show here that the catalytic subunit of TAK is a known human kinase previously named PITALRE, which is a member of the cyclin-dependent family of proteins...
  71. 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...
  72. pmc PITALRE, the catalytic subunit of TAK, is required for human immunodeficiency virus Tat transactivation in vivo
    M O Gold
    Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Virol 72:4448-53. 1998
    The human cdc2-related kinase PITALRE is the catalytic component of TAK, the Tat-associated kinase. Previously, we have proposed that TAK is a cellular factor that mediates Tat transactivation function...
  73. 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...
  74. 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...
  75. ncbi Physical interaction between CDK9 and B-Myb results in suppression of B-Myb gene autoregulation
    G De Falco
    Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Oncogene 19:373-9. 2000
    ..We report in this study that CDK9, the cyclin T associated kinase, which phosphorylates and activates RNA-Polymerase II, suppresses B-Myb ..
  76. ncbi Genomic organization and characterization of promoter function of the human CDK9 gene
    H Liu
    Division of Molecular Virology, Baylor College of Medicine, One Baylor Plaza, 77030, Houston, TX, USA
    Gene 252:51-9. 2000
    b>CDK9 is the catalytic subunit of a general RNA polymerase II (RNAP II) elongation factor termed p-TEFb which is targeted by the human immunodeficiency virus (HIV) Tat protein to activate elongation of the integrated proviral genome...
  77. pmc 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
    Y W Fong
    Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720 3206, USA
    Mol Cell Biol 20:5897-907. 2000
    ..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 ..
  78. 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...
  79. 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...
  80. 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...
  81. 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...
  82. 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...
  83. ncbi Three cyclin-dependent kinases preferentially phosphorylate different parts of the C-terminal domain of the large subunit of RNA polymerase II
    Reena Pinhero
    Department of Molecular Biology and Genetics, University of Guelph, Ontario, Canada
    Eur J Biochem 271:1004-14. 2004
    ..regulated by the phosphorylation of the CTD by three cyclin-dependent protein kinases (CDKs), namely CDK7, CDK8 and CDK9. In this study, we systematically compared the phosphorylation of different recombinant CTD substrates by ..
  84. ncbi Differential localization and expression of the Cdk9 42k and 55k isoforms
    Hongbing Liu
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Cell Physiol 203:251-60. 2005
    ..There are two known isoforms of Cdk9: a 42 kDa protein (42k, originally identified as PITALRE) and a more recently identified 55 kDa form (55k)...
  85. ncbi HIV-1 TAR RNA: the target of molecular interactions between the virus and its host
    Sylvie Bannwarth
    McGill University AIDS Centre, Molecular Oncology Group, Lady Davis Institute for Medical Research, Canada
    Curr HIV Res 3:61-71. 2005
    ..The Tat-Cyclin T1-CDK9 complex is the main component in the trans-activation of HIV-1 and its affinity for TAR is regulated through Tat ..
  86. pmc A new paradigm in eukaryotic biology: HIV Tat and the control of transcriptional elongation
    Matjaz Barboric
    Department of Medicine, Rosalind Russell Medical Research Center, University of California, San Francisco, USA
    PLoS Biol 3:e76. 2005
  87. 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...
  88. 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...
  89. pmc LARP7 is a stable component of the 7SK snRNP while P-TEFb, HEXIM1 and hnRNP A1 are reversibly associated
    Brian J Krueger
    Molecular and Cellular Biology Program, University of Iowa, Iowa City, Iowa, USA
    Nucleic Acids Res 36:2219-29. 2008
    ..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...
  90. 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...
  91. 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...
  92. 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...
  93. 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...
  94. 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 ..
  95. 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...
  96. 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...
  97. 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
    ....
  98. pmc CDK9 regulates AR promoter selectivity and cell growth through serine 81 phosphorylation
    Vicki Gordon
    University of Virginia, Department of Microbiology, Charlottesville, Virginia 22908, USA
    Mol Endocrinol 24:2267-80. 2010
    ..We observed cyclin-dependent kinase (CDK)9 association with the AR. CDK9 phosphorylates the AR on S81 in vitro...
  99. 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...
  100. 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...
  101. 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 ..

Research Grants66

  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. BORIS MATIJA PETERLIN; Fiscal Year: 2015
    ..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. Qiang Zhou; Fiscal Year: 2016
    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...
  6. 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-..
  7. Maha Abdellatif; Fiscal Year: 2016
    ..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...
  8. Geoffrey I Shapiro; Fiscal Year: 2014
    ..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. 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 ..
  10. Lin Feng Chen; Fiscal Year: 2015
    ..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. Katherine A Jones; Fiscal Year: 2016
    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...
  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
    ..Therefore, the second aim will study if iron chelators inhibit expression and cellular activities of the cyclin dependent kinase 9 (CDK9) and CDK2...
  17. 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...
  18. Arno L Greenleaf; Fiscal Year: 2014
    ..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...
  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. 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 ..
  21. 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...
  22. ZAHRA TOOSSI TOOSSI; Fiscal Year: 2014
    ..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...
  23. DAVID SUNG WEN YU; Fiscal Year: 2014
    ..in human cells to identify 14 high-confidence RSR genes, including the novel RSR gene, cyclin-dependent kinase 9 (CDK9)...
  24. 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...
  25. Fatah Kashanchi; Fiscal Year: 2015
    ..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...
  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. MECHANISMS OF HIV1 TAT TRANSACTIVATION
    David Price; Fiscal Year: 2001
    ..First, human P-TEFb will be characterized by determining its subunit structure. PITALRE, the kinase subunit, and several putative cyclin subunits will be analyzed to determine if they are in complexes ..
  32. 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...
  33. Regulation of P-TEFb during HIV Infection
    David Price; Fiscal Year: 2005
    ..P-TEFb is a cyclin dependent kinase comprised of Cdk9 and one of several possible cyclin subunits and Tat recruits only P-TEFb containing cyclinTI...
  34. 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...
  35. 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 ..
  36. Andrei E Medvedev; Fiscal Year: 2014
    ..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 ..
  37. 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 ..
  38. Curry L Koening; Fiscal Year: 2016
    ..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...
  39. DAVID SUNG WEN YU; Fiscal Year: 2016
    ..Recent data from the lab show that SIRT2 deacetylates CDK9 at a conserved lysine residue to promote recovery from replication arrest...
  40. 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...
  41. 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...
  42. Richard W Carthew; Fiscal Year: 2014
    ..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 ..
  43. Slava Epelman; Fiscal Year: 2014
    ..The PI will tak advantage of this mentorship and the enormous basic science and clinical resources available at Washington ..
  44. 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...
  45. Role of adipocytes in local and systemic inflammation
    Chantal A Rivera; Fiscal Year: 2010
    ..b>Tak Yee Aw and Dr. Mathew Grisham...
  46. Maha Abdellatif; Fiscal Year: 2014
    ..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...
  47. 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 ..
  48. 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...
  49. 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 ..
  50. 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...
  51. Theresa Louise Bender Pape; Fiscal Year: 2014
    ..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...
  52. 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...
  53. Daniel R Kuritzkes; Fiscal Year: 2016
    ..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...
  54. 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...
  55. 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...
  56. 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...
  57. 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...
  58. 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-..
  59. 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...
  60. 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...
  61. 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'-..
  62. 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...
  63. 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 ..
  64. 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...
  65. 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 ..
  66. 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...