       Document 0593
 DOCN  M9460593
 TI    Convergence of multiple nuclear receptor signaling pathways onto the
       long terminal repeat of human immunodeficiency virus-1.
 DT    9404
 AU    Ladias JA; Department of Medicine, New England Deaconess Hospital,
       Harvard; Medical School, Boston, Massachusetts 02215.
 SO    J Biol Chem. 1994 Feb 25;269(8):5944-51. Unique Identifier : AIDSLINE
       MED/94164952
 AB    A composite element that interacts with multiple nuclear receptors has
       been identified in the long terminal repeat (LTR) of the human
       immunodeficiency virus-1 (HIV-1). This element, designated nuclear
       receptor-responsive element (NRRE), spans the 356 to -320 LTR region and
       contains tightly clustered binding sites for the retinoid X
       receptor-alpha (RXR alpha) and for five nuclear receptors with unknown
       ligands, apolipoprotein AI regulatory protein-1 (ARP-1), v-erbA-related
       proteins-2 and -3 (EAR-2 and EAR-3), hepatocyte nuclear factor-4
       (HNF-4), and nerve growth factor-inducible protein-B (NGFI-B). The NRRE
       also interacts with heterodimers formed between RXR alpha and either
       ARP-1, EAR-2, EAR-3, the retinoic acid receptor-alpha (RAR alpha), or
       the peroxisome proliferator-activated receptor (PPAR). Remarkably,
       nuclear receptor binding is conserved in the LTRs of recently evolved
       HIV-1 strains but it is absent in the oldest and most divergent viral
       isolates, raising the intriguing possibility that the NRRE has been
       evolved recently in the viral genome. Cotransfection experiments in
       human choriocarcinoma JEG-3 cells have shown that the HIV-1 LTR-driven
       transcription is activated by RXR alpha and RAR alpha in the presence of
       9-cis- and all-trans-retinoic acid, by PPAR and RXR alpha in the
       presence of clofibric acid and 9-cis-retinoic acid, and by the orphan
       receptors HNF-4 and NGFI-B. These findings suggest that a complex
       network of nuclear receptor signaling pathways, that include 9-cis- and
       all-trans-retinoic acid, fatty acids, peroxisome proliferators, growth
       factors, membrane depolarization, and possibly other signals, converge
       onto the HIV-1 NRRE and may participate in modulation of viral gene
       expression.
 DE    Base Sequence  DNA, Viral/*METABOLISM  Human  *HIV Long Terminal Repeat
       HIV-1/GENETICS/*METABOLISM  Molecular Sequence Data  Receptors,
       Cytoplasmic and Nuclear/*METABOLISM  *Signal Transduction  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Transcription, Genetic
       Tumor Cells, Cultured  JOURNAL ARTICLE

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

