Document 0598
 DOCN  M9550598
 TI    Lentivirus Tat proteins specifically associate with a cellular protein
       kinase, TAK, that hyperphosphorylates the carboxyl-terminal domain of
       the large subunit of RNA polymerase II: candidate for a Tat cofactor.
 DT    9505
 AU    Herrmann CH; Rice AP; Division of Molecular Virology, Baylor College of
       Medicine,; Houston, Texas 77030-3498.
 SO    J Virol. 1995 Mar;69(3):1612-20. Unique Identifier : AIDSLINE
       MED/95156588
 AB    Efficient replication of human immunodeficiency virus types 1 and 2
       (HIV-1 and HIV-2) requires the virus transactivator proteins known as
       Tat. In order to understand the molecular mechanisms involved in Tat
       transactivation, it is essential to identify the cellular target(s) of
       the Tat activation domain. Using an in vitro kinase assay, we previously
       identified a cellular protein kinase activity, Tat-associated kinase
       (TAK), that specifically binds to the activation domains of Tat
       proteins. Here it is demonstrated that TAK fulfills the genetic criteria
       established for a Tat cofactor. TAK binds in vitro to the activation
       domains of the Tat proteins of HIV-1 and HIV-2 and the distantly related
       lentivirus equine infectious anemia virus but not to mutant Tat proteins
       that contain nonfunctional activation domains. In addition, it is shown
       that TAK is sensitive to dichloro-1-beta-D-ribofuranosylbenzimidazole, a
       nucleoside analog that inhibits a limited number of kinases and is known
       to inhibit Tat transactivation in vivo and in vitro. We have further
       identified an in vitro substrate of TAK, the carboxyl-terminal domain of
       the large subunit of RNA polymerase II. Phosphorylation of the
       carboxyl-terminal domain has been proposed to trigger the transition
       from initiation to active elongation and also to influence later stages
       during elongation. Taken together, these results imply that TAK is a
       very promising candidate for a cellular factor that mediates Tat
       transactivation.
 DE    Cell Nucleus/ENZYMOLOGY  Dichlororibofuranosylbenzimidazole/PHARMACOLOGY
       *Gene Expression Regulation, Viral  Gene Products, tat/*METABOLISM  Hela
       Cells/ENZYMOLOGY  Human  HIV-1/METABOLISM  HIV-2/METABOLISM
       Phosphorylation  Protein Binding  Protein Kinases/ANTAGONISTS &
       INHIB/*METABOLISM  RNA Polymerase II/*METABOLISM  Signal Transduction
       Support, U.S. Gov't, P.H.S.  Transcription, Genetic  JOURNAL ARTICLE

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