       Document 0999
 DOCN  M9620999
 TI    NF-kappa B site-mediated negative regulation of the HIV-1 promoter by
       CCAAT/enhancer binding proteins in brain-derived cells.
 DT    9602
 AU    Mondal D; Alam J; Prakash O; Department of Molecular Oncology, Alton
       Ochsner Medical; Foundation, New Orleans, LA 70121, USA.
 SO    J Mol Neurosci. 1994-95;5(4):241-58. Unique Identifier : AIDSLINE
       MED/96101971
 AB    Several transcription regulatory elements that interact with cellular
       DNA-binding proteins have been identified in the HIV-1 long terminal
       repeat (LTR). We have identified two sequence motifs in the U3 region of
       the LTR that are similar to the consensus 9-bp DNA-binding element of
       the CCAAT/enhancer-binding protein (C/EBP) family of transcription
       factors. One of the sequences (promoter-proximal) mapped immediately
       upstream of the NF-kappa B element, whereas the other (promoter-distal)
       completely overlapped the upstream stimulatory factor (USF) binding
       site. In this study, we investigated the role of the enhancer-proximal
       consensus C/EBP binding sequence in the expression of the HIV-1 LTR. In
       cotransfection assays we found that although this sequence is a
       functional C/EBP-responsive element, the regulation of the HIV promoter
       by C/EBP is very complex. C/EBP isoforms inhibited the phorbol
       12-myristate 13-acetate (PMA)-stimulated HIV-1 promoter activity in
       human glioblastoma U138MG and neuroblastoma SHSY5Y cells, but not in
       HeLa epithelial cells, and this inhibition required the NF-kappa B
       element. C/EBP also downregulated the HIV NF-kappa B element-containing
       SV40 early promoter activity, regardless of the presence of the flanking
       C/EBP-binding sequences, in the two brain-derived cells. In
       electrophoretic mobility shift assays with nuclear extracts from HeLa
       and U138MG cells, purified C/EBP markedly increased the complex
       formation between endogenous proteins and the NF-kappa B DNA probe
       without detectable association with the complex. However, with extracts
       from U138MG cells but not from HeLa cells, a slow migrating complex was
       observed. Our data suggest that the C/EBP family of transcription
       factors can downregulate the HIV-1 promoter activity in CNS-derived
       cells through the NF-kappa B binding elements.
 DE    Animal  Base Sequence  Brain/*CYTOLOGY  Consensus Sequence  DNA-Binding
       Proteins/*METABOLISM  DNA, Viral/METABOLISM  *Gene Expression
       Regulation, Viral  Genes, Reporter  Glioblastoma/PATHOLOGY  Hela Cells
       Human  *HIV Long Terminal Repeat  HIV-1/*GENETICS  Macromolecular
       Systems  Mice  Molecular Sequence Data  Neuroblastoma/PATHOLOGY  Nuclear
       Proteins/*METABOLISM  NF-kappa B/*PHYSIOLOGY  *Promoter Regions
       (Genetics)  Protein Binding  Recombinant Fusion Proteins/BIOSYNTHESIS
       Regulatory Sequences, Nucleic Acid  Support, Non-U.S. Gov't
       Tetradecanoylphorbol Acetate/PHARMACOLOGY  Transfection  Tumor Cells,
       Cultured  JOURNAL ARTICLE

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

