title: Binding of NF-kB to the HIV-1 LTR is not sufficient to induce HIV-1 LTR activity.
abstract: Human immunodeficiency virus type 1 (HIV-1) spends a significant part of its life cycle as latent provirus in nonactivated cells. It induction requires mitogen stimulation. TPA treatment induces HIV-1 transcription by protein kinase C (PKC)-mediated activation of the cellular transcription factor NF-kB. PKC activation induces the dissociation of NF-kB from its inhibitor protein (IkB). The liberated NF-kB then binds to its proviral recognition sequence in the HIV-1 long terminal repeat (LTR) sequence. This step, however, is not sufficient to augment transcription. We demonstrate that NF-kB-mediated HIV-1 LTR activation is regulated by an additional event that is not dependent on IkB. A further phosphorylation event is proposed, since this step could be blocked by an inhibitor of a phospholipase C (PLC) type reaction. This inhibitor precludes the formation of diacylglycerols, which are required for activation of PKC isoenzymes. As an alternative pathway that is not dependent on PLC reactions, high-level transcription from the HIV-1 LTR is shown to require binding of both NF-kB and TAT.
authors.affiliation: German Cancer Research Center, Institute for Virus Research, Heidelberg.
authors.forename: C
authors.initials: C
authors.lastname: Doppler
authors.forename: G
authors.initials: G
authors.lastname: Schalasta
authors.forename: E
authors.initials: E
authors.lastname: Amtmann
authors.forename: G
authors.initials: G
authors.lastname: Sauer
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D001483:Base Sequence; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase; D015342:DNA Probes; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015696:Gene Products, tat; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D006367:HeLa Cells; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009636:Norbornanes; D010879:Piperazines / Q000494:pharmacology; D010957:Plasmids; D011493:Protein Kinase C / Q000378:metabolism; D011533:Proviruses / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D014162:Transfection; D014775:Virus Activation; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D001952:Bridged-Ring Compounds; D015342:DNA Probes; D015696:Gene Products, tat; D007546:Isoquinolines; D016328:NF-kappa B; D009636:Norbornanes; D010879:Piperazines; D013859:Thiocarbamates; D013871:Thiones; D054322:tat Gene Products, Human Immunodeficiency Virus; C046498:tricyclodecane-9-yl-xanthogenate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015500:Chloramphenicol O-Acetyltransferase; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate