Document 0068
 DOCN  M9550068
 TI    A CNS-enriched factor that binds to NF-kappa B and is required for
       interaction with HIV-1 tat.
 DT    9505
 AU    Taylor JP; Pomerantz RJ; Oakes JW; Khalili K; Amini S; Jefferson
       Institute of Molecular Medicine, Department of; Biochemistry and
       Molecular Biology, Thomas Jefferson University,; Philadelphia,
       Pennsylvania 19107.
 SO    Oncogene. 1995 Jan 19;10(2):395-400. Unique Identifier : AIDSLINE
       MED/95140429
 AB    The Human Immunodeficiency Virus type 1 (HIV-1) Tat protein is a potent
       activator of transcription directed by the long terminal repeat (LTR),
       an essential step in the life-cycle of HIV-1. While interaction of Tat
       with an RNA element encoded by downstream LTR sequences (termed TAR) is
       commonly considered essential to activation, numerous recent reports
       have implicated upstream transcription elements within the LTR as
       participants in mediating this activation. We have recently demonstrated
       that Tat activation occurs independent of the TAR element in certain
       cells derived from the central nervous system (CNS), and that this
       activation is mediated by the kappa B domain of the LTR. Further,
       CNS-derived cells were found to contain kappa B-binding activity capable
       of both interacting with Tat and activating LTR transcription in vitro.
       The present study demonstrates that the kappa B-binding transcription
       factor derived from CNS cells consists of a component indistinguishable
       from prototypical Nuclear Factor-kappa B (NF-kappa B) (in size, mobility
       on native gel, kinetics of activation and cognate binding sequence) as
       well as a supershifting component that is dissociable under certain
       conditions. The supershifting activity is found to stabilize binding of
       the presumed NF-kappa B to DNA. Further, only the form of NF-kappa B
       which is associated with this supershifting activity is capable of
       binding Tat. We hypothesize a model in which Tat utilizes this
       interaction to activate HIV-1 through the NF-kappa B domain of the LTR
       in circumstances where TAR is absent. This model has implications with
       respect to the ability of Tat to alter cellular gene expression and
       perhaps contribute to the array of problems seen in HIV-1 infection such
       as altered immune status, CNS toxicity, and the formation of tumors.
 DE    Astrocytes/*METABOLISM  Base Sequence  Electrophoresis, Gel,
       Two-Dimensional  Gene Products, tat/*PHYSIOLOGY  HIV-1/*PHYSIOLOGY
       Models, Genetic  Molecular Sequence Data  NF-kappa B/*METABOLISM
       Repetitive Sequences, Nucleic Acid  Support, U.S. Gov't, P.H.S.
       Trans-Activation (Genetics)  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).