       Document 0857
 DOCN  M9480857
 TI    The upregulation of the promoter gene encoding the p105/p50 subunit of
       NF-kB by HIV is dependent upon one specific kB motif.
 DT    9410
 AU    Ten R; MacMorran W; Rolli V; Israel A; Paya C; Division of Experimental
       Pathology, Mayo Clinic, Rochester, MN; 55905.
 SO    Abstr Gen Meet Am Soc Microbiol. 1994;94:483 (abstract no. T-5). Unique
       Identifier : AIDSLINE ASM94/94313088
 AB    Our previous cloning and sequencing of the promoter of the gene encoding
       the p50 subunit of NF-kB indicated that it is upregulated by NF-kB.
       Furthermore, we have shown that in persistently HIV-infected monocytic
       cells, which contain increased NF-kB activity, the transcriptional
       regulation of this promoter is increased. We have further characterized
       the different regulatory sequences of the p105/p50 promoter that could
       potentially participate in its autoregulation. One AP-1, four NF-kB like
       and one HIP-1 motifs are present in this promoter. Gel shift analysis
       using nuclear extracts from monocytic cells unstimulated or treated with
       LPS or HIV-infected demonstrated specific binding proteins to the AP-1
       site, to the three of the four kB sites, but not to the HIP-1 motif. One
       of the three kB sites (kB4) bound NF-kB complexes with higher affinity
       than the rest. Deletion and mutation constructs of the p105 promoter
       cloned upstream a luciferase reporter gene followed by transfection into
       monocytic cells was performed. The AP-1, kB1, kB2, kB3, and HIP-1
       regions were found to be dispensable for the basal and LPS-inducible
       transcriptional activity of the promoter in uninfected and HIV-infected
       monocytes. Only the kB4 site was identified as essential in the
       regulation of the p105 promoter. These results suggest that the p105/p50
       promoter is solely regulated by NF-kB complexes binding with high
       affinity to only one of the kB motifs in monocytic cells.
 DE    Binding Sites  *Gene Expression Regulation, Viral  Human  HIV/*GENETICS
       Lipopolysaccharides/PHARMACOLOGY  Luciferase/BIOSYNTHESIS
       Monocytes/DRUG EFFECTS/*METABOLISM/MICROBIOLOGY  NF-kappa
       B/BIOSYNTHESIS/*GENETICS/METABOLISM  *Promoter Regions (Genetics)
       Recombinant Proteins/BIOSYNTHESIS  Transcription, Genetic  Transfection
       MEETING ABSTRACT

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

