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 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
  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. 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
  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. 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
  6. 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
  7. pmc RNA-mediated displacement of an inhibitory snRNP complex activates transcription elongation
    Iván D'Orso
    Department of Biochemistry and Biophysics, University of California, San Francisco, California, USA
    Nat Struct Mol Biol 17:815-21. 2010
  8. 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
  9. 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
  10. 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

Detail Information

Publications238 found, 100 shown here

  1. 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...
  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. 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...
  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. 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)...
  6. 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...
  7. pmc RNA-mediated displacement of an inhibitory snRNP complex activates transcription elongation
    Iván D'Orso
    Department of Biochemistry and Biophysics, University of California, San Francisco, California, USA
    Nat Struct Mol Biol 17:815-21. 2010
    ..Recruitment of an inhibitory snRNP complex at an early stage in the transcription cycle provides a new paradigm for controlling gene expression with a noncoding RNA...
  8. 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...
  9. 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...
  10. 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...
  11. 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...
  12. 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...
  13. 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...
  14. 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...
  15. 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 ..
  16. 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)...
  17. 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...
  18. 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 ..
  19. 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...
  20. 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...
  21. 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...
  22. 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...
  23. 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...
  24. 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 ..
  25. 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...
  26. 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 ..
  27. 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 ..
  28. 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)...
  29. 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...
  30. 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
    ....
  31. 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...
  32. 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)...
  33. 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...
  34. 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...
  35. 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...
  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 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...
  38. 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...
  39. 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...
  40. 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...
  41. 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...
  42. 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...
  43. 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 ..
  44. 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...
  45. 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/..
  46. 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...
  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 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...
  49. 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
    ....
  50. 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...
  51. 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)...
  52. 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 ..
  53. 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...
  54. 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.
  55. 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
    ....
  56. 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...
  57. 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...
  58. 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...
  59. 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-..
  60. 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
    ....
  61. 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...
  62. 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...
  63. 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...
  64. 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...
  65. 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...
  66. 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 ..
  67. 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...
  68. 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...
  69. 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...
  70. 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...
  71. 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...
  72. 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 ..
  73. 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...
  74. 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)...
  75. 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...
  76. ncbi HIV-1 infection and regulation of Tat function in macrophages
    Li Ying Liou
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Int J Biochem Cell Biol 36:1767-75. 2004
    ..The viral Tat protein, whose function is mediated by the cellular cyclin T1 protein complexed with CDK9, is required for efficient transcription of the integrated HIV-1 provirus by RNA polymerase II...
  77. 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...
  78. ncbi HIV-1 Tat interacts with cyclin T1 to direct the P-TEFb CTD kinase complex to TAR RNA
    M E Garber
    Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037 1099, USA
    Cold Spring Harb Symp Quant Biol 63:371-80. 1998
  79. 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...
  80. 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...
  81. 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...
  82. 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...
  83. 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 ..
  84. ncbi Compensatory contributions of HEXIM1 and HEXIM2 in maintaining the balance of active and inactive positive transcription elongation factor b complexes for control of transcription
    Jasper H N Yik
    Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA
    J Biol Chem 280:16368-76. 2005
    ..Our results demonstrate that there is a tightly regulated cellular process to maintain the balance between active and inactive P-TEFb complexes, which controls global transcription as well as cell growth and differentiation...
  85. ncbi The functional role of an interleukin 6-inducible CDK9.STAT3 complex in human gamma-fibrinogen gene expression
    Tieying Hou
    Department of Biochemistry, and Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Texas 77555 1060, USA
    J Biol Chem 282:37091-102. 2007
    ..of the APR, we investigated the requirement of an IL-6-inducible complex of STAT3 with cyclin-dependent kinase 9 (CDK9) on gamma-FBG expression in HepG2 hepatocarcinoma cells...
  86. 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...
  87. 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...
  88. pmc Tat modifies the activity of CDK9 to phosphorylate serine 5 of the RNA polymerase II carboxyl-terminal domain during human immunodeficiency virus type 1 transcription
    M Zhou
    Virus Tumor Biology Section, LRBGE, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA
    Mol Cell Biol 20:5077-86. 2000
    ..Our results demonstrate that cyclin-dependent kinase 7 (CDK7) (TFIIH) and CDK9 (P-TEFb) both associate with the HIV-1 preinitiation complex...
  89. 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 ..
  90. ncbi Direct evidence that HIV-1 Tat stimulates RNA polymerase II carboxyl-terminal domain hyperphosphorylation during transcriptional elongation
    C Isel
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK
    J Mol Biol 290:929-41. 1999
    ..inhibited by low concentrations of 5,6-dichloro-1-beta- D -ribofuranosyl benzimidazole (DRB), a potent inhibitor of CDK9, the protein kinase subunit of the Tat-associated kinase (TAK)...
  91. 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...
  92. 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...
  93. 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...
  94. 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
  95. 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...
  96. 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) ..
  97. 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...
  98. 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...
  99. 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...
  100. 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...
  101. ncbi Interaction of Sp1 transcription factor with HIV-1 Tat protein: looking for cellular partners
    Arianna Loregian
    Department of Histology, Microbiology and Medical Biotechnologies, University of Padova, Via Gabelli 63, 35121, Padua, Italy
    FEBS Lett 543:61-5. 2003
    ..proteins recently shown to play a relevant role in Tat function, namely TATA box-binding protein, cyclin T1, CDK9, and cyclin T1/CDK9 complex, were coexpressed, individually or in pair-wise combination, with Tat and Sp1 hybrids...

Research Grants27

  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. 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...
  3. 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 ..
  4. 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...
  5. 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...
  6. Tat Transactivation
    BORIS MATIJA PETERLIN; Fiscal Year: 2013
    ..Importantly, CycK does not bind Cdk9, which together with CycT1 or CycT2 forms P-TEFb...
  7. 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...
  8. 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-..
  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. 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...
  12. 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...
  13. 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...
  14. 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 ..
  15. 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...
  16. 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...
  17. 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)...
  18. 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...
  19. 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...
  20. 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...
  21. 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...
  22. 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 ..
  23. 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 ..
  24. 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 ..
  25. 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...
  26. 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)...
  27. 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...