2nd National Conference Human Retroviruses and Related Infections Washington, DC - January 29 - February 2, 1995

Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 25)

Herrmann CH, Rice AP
Baylor College of Medicine, Houston, TX 77030

Efficient replication of human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) requires the viral 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 have previously identified a cellular protein kinase activity, termed TAK, for Tat-associated kinase, that specifically binds to the activation domains of the Tat proteins. We have recently found 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,HIV-2, and the distantly related lentivirus equine infectious anemia virus, but not to mutant Tat proteins that contain nonfunctional activation domains. In addition, we have found that TAK is sensitive to DRB, 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 (CTD) of the large subunit of RNA polymerase II. Phosphorylation of the CTD has been proposed to trigger the transition from initiation to active elongation and also to influence later stages during elongation. Together, these results implicate TAK as a very promising candidate for a cellular factor that mediates Tat transactivation. We are currently attempting to purify TAK and investigate its role in Tat function.

Keywords: Animals, Gene Products, tat, Genes, tat, HIV-1, HIV-2, Humans, In Vitro, Phosphorylation, Positive Transcriptional Elongation Factor B, Protein Kinases, RNA Polymerase II, Trans-Activation (Genetics), Trans-Activators, Transcription, Genetic, genetics

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1995-01-29
25

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