Regulation of HIV-Tat and Nef by PAK4 kinase and its binding partners and methods of identifying modulators thereof

摘要

The present invention discloses complexes of cellular signaling proteins that interact in vivo with the HIV-encoded auxiliary proteins Nef and Tat to modulate their activity. This complex includes the novel serine/threonine kinase PAK4 and the novel guanine nucleotide exchange factor Cdc42-GEF, which synergize to stimulate Tat transcriptional activity, and the acetyl-transferase Tip60 which modifies Nef. These cellular partners of the HIV auxiliary proteins represent novel targets for HIV therapeutics. The invention provides isolated DNA and vectors encoding PAK4 and Cdc42-GEF, and methods of producing recombinant forms of these proteins. The invention also provides methods for identifying compounds that modulate the activity of HIV-Tat, HIV-Nef or Tip60, and methods for modulating the activity of these enzymes.