Purification of a Tat-associated kinase reveals a TFIIH complex that modulates HIV-1 transcription

The EMBO Journal
L F García-MartínezR B Gaynor

Abstract

The Tat protein is a transcriptional activator which is required for efficient human immunodeficiency virus 1 (HIV-1) gene expression Tat stimulates HIV-1 transcriptional elongation by increasing the processivity of RNA polymerase II. To address whether Tat-mediated effects on HIV-1 gene expression are due to modulation in the phosphorylation of the RNA polymerase II C-terminal domain (CTD), we developed a purification protocol to identify cellular kinases that are capable of binding to Tat and hyperphosphorylating the RNA polymerase II CTD. A 600 kDa protein complex with these properties was isolated, and specific components were identified using peptide microsequence analysis. This analysis indicated that proteins comprising the multi-subunit TFIIH complex, in addition to several novel factors, were associated with Tat using both in vitro and in vivo analysis. The Tat-associated kinase bound to the activation domain of Tat, and its ability to hyperphosphorylate RNA polymerase II was markedly stimulated by Tat. Furthermore, the addition of the Tat-associated kinase to in vitro transcription assays stimulated the ability of Tat to activate HIV-1 transcription. These results define a cellular kinase complex whose activity is mod...Continue Reading

References

Nov 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·H LuD Reinberg
May 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·M B FeinbergA D Frankel
Sep 12, 1995·Proceedings of the National Academy of Sciences of the United States of America·J P TassanE A Nigg
Jan 1, 1995·Annual Review of Biochemistry·L Zawel, D Reinberg
Mar 1, 1995·Trends in Biochemical Sciences·A J Koleske, R A Young
May 23, 1995·Proceedings of the National Academy of Sciences of the United States of America·T P MäkeläR A Weinberg
Jul 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·M A GraebleJ Karn
Jun 25, 1996·Proceedings of the National Academy of Sciences of the United States of America·J T ReardonZ Q Pan
Jun 25, 1996·Proceedings of the National Academy of Sciences of the United States of America·R DrapkinD Reinberg
Mar 5, 1996·Proceedings of the National Academy of Sciences of the United States of America·G MavankalR B Gaynor

❮ Previous
Next ❯

Citations

Mar 21, 2001·Biochimica Et Biophysica Acta·J D WeissmanD S Singer
Jul 4, 1998·Current Biology : CB·K Yankulov, D Bentley
Sep 5, 2001·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·A FukudaK Hisatake
Jun 30, 2005·Animal Health Research Reviews·Marie-Claude St-LouisDenis Archambault
Mar 13, 2012·AIDS Research and Human Retroviruses·Natallia DziubaJames L Murray
Jun 29, 1999·Cold Spring Harbor Symposia on Quantitative Biology·S McCrackenD Bentley
Mar 25, 2000·Molecular and Cellular Biology·D H Price
Oct 6, 1998·Annual Review of Biochemistry·A D Frankel, J A Young
Feb 9, 2005·Retrovirology·Nicolas EpieSergei Nekhai
Nov 11, 2005·Retrovirology·John Brady, Fatah Kashanchi
May 21, 2009·Retrovirology·Virginie W GautierWilliam W Hall
Jul 28, 2009·Virology Journal·Irene GuendelKylene Kehn-Hall
Mar 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Kristine YoderRichard Fishel
Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·H XiaoR G Roeder
Jul 8, 1999·Proceedings of the National Academy of Sciences of the United States of America·P D BieniaszB R Cullen
Mar 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·J NevadoM Ptashne
Feb 7, 1998·Proceedings of the National Academy of Sciences of the United States of America·J ArchambaultJ Greenblatt
Sep 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·J D WeissmanD S Singer
Aug 2, 2002·Expert Opinion on Investigational Drugs·Roger G Ptak
Aug 21, 2013·Chemical Reviews·Dirk Eick, Matthias Geyer
Aug 18, 2012·Advances in Virology·Luna LiBrian Wigdahl
Nov 28, 2000·Annual Review of Genetics·T I Lee, R A Young
May 18, 1999·Archives of Biochemistry and Biophysics·T M Rana, K T Jeang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.