NFBP is a novel cellular protein discovered due to its ability to bind to NF-kB subunits, specifically p50 and p65. NF-kappaB represents a family of inducible DNA-binding transcription factors whose activity is critical for expression of the HIV-1 genome. Our results demonstrate that in human astrocytic cells, U-87MG,NFBP activates the HIV-1 LTR promoter via the NF-kB responsive element position between -117 to -80relative to the transcription start site of the HIV-1 LTR and that induction of NF-kappaB subunits enhances the level of activation of the HIV-1 LTR by NFBP. Furthermore, NFBP exhibits the capacity to bind to the HIV-1transactivator protein, Tat. This interaction is functional as NFBP augments the activation of the HIV-1 LTR by tat. In this KO1 grant application, we hypothesize that communication between NFBP with NF-kappaB and tat plays an important role in transcriptional activation and replication of the HIV-1 genome in human astrocytes, microglia, macrophage/monocytic cells and T-cells. We will perform comprehensive studies to identify the mechanisms by which NFBP activates basal and tat mediated activation of HIV-1 transcription via NF-kappaB; and map the region of NFBP that is necessary for HIV-1 activation in the presence and absence of NF-kappaB subunits by creating and utilizing deletion mutants of NFBP. Further, we will examine the effects of NFBP on viral infection and determine the subcellular localization of NFBP before and after induction of NF-kB subunits in various cells as well as during the course of viral infection. As our preliminary data demonstrate the ability of NFBP to associate with NF-kappaB subunits through RNA molecules, we will employ various protein-protein interaction techniques and PCR amplification to identify the RNA species that mediates the NFBP: NF-kappaB association and examine its biological effects upon viral gene expression by NFBP, NF-kB and tat in the various cell types. The results of these studies should provide critical and novel information on the events involved in control of HIV-1 gene expression in CNS as well as lymphocytic cells.
| Sweet, Thersa; Yen, William; Khalili, Kamel et al. (2008) Evidence for involvement of NFBP in processing of ribosomal RNA. J Cell Physiol 214:381-8 |
| Sweet, Thersa; Sawaya, Bassel E; Khalili, Kamel et al. (2005) Interplay between NFBP and NF-kappaB modulates tat activation of the LTR. J Cell Physiol 204:375-80 |
