TI  - Interaction between cell cycle regulator,  <prot>E2F-1</prot> , and  <prot>NF-kappaB</prot>  mediates
      repression of HIV-1 gene transcription.
PG  - 29468-74
AB  - The <prot>NF-kappaB</prot>/<prot>Rel</prot> family of transcription factors is one of the main
      targets of cytokines and other agents that induce HIV-1 gene expression.
      Some of these extracellular stimuli arrest cells in the G1 phase of the
      mitotic division cycle and modulate the activity of the tumor suppressor
      protein <prot>Rb</prot> and its partner <prot>E2F-1</prot>. Earlier studies indicated that <prot>E2F-1</prot>, a
      transcription factor that stimulates expression of S-phase-specific genes,
      is able to repress transcription directed by the human immunodeficiency
      virus (HIV-1) type-1 promoter in a variety of cells, including those of
      glial and lymphocytic origin. Here, we demonstrate that   <prot>E2F-1</prot>   may regulate
      the activity of the HIV-1 long terminal repeat through its ability to bind
      sequences in the  <prot>NF-kappaB</prot>  enhancer region and to interact with the
      <prot>NF-kappaB</prot> subunit,  <prot>p50</prot> . Gel retardation and methylation interference
      assays show that  <prot>E2F-1</prot>  is able to bind specifically to a site embedded
      within the two  <prot>NF-kappaB</prot>  elements. Gel retardation/immunoblot analysis
      using purified <prot>E2F-1</prot> and <prot>p50</prot> homodimers reveals the presence of complexes
      containing both proteins. Affinity chromatography and
      co-immunoprecipitation assays provide evidence for direct interaction of
       <prot>E2F-1</prot>  and  <prot>p50</prot>  in the absence of their DNA target sequences. In vitro
      transcription assay demonstrates that <prot>E2F-1</prot> represses <prot>NF-kappaB</prot> mediated
      transcription in a cell-free system. Functional studies in Jurkat T
      lymphocytic cells point to the importance of both the <prot>E2F</prot> and <prot>NF-kappaB</prot>
      binding sites in <prot>E2F-1</prot> mediated repression of HIV-1 promoter, in vivo. The
      results of this study suggest that  <prot>NF-kappaB</prot>  activity may be regulated by
      its interaction with the cell cycle regulatory protein,  <prot>E2F-1</prot> .
AD  - Center for NeuroVirology and NeuroOncology, and Department of Neurology,
