title: NF-kappaB activation upon interaction of HIV-1 envelope glycoproteins with cell surface CD4 involves IkappaB kinases.
abstract: Human immunodeficiency virus type-1 envelope glycoprotein (gp120(env)) binding to cell surface CD4 receptor triggers a broad range of intracellular effects leading to T cell activation and cell cycle entry. Among these effects we and others previously reported on the nuclear translocation of the nuclear factor-kappaB (NF-kappaB) transcription factor. The present work further investigates the signal transduction pathways involved in gp120(env)-induced NF-kappaB activation. We demonstrate that gp120(env)-CD4 interaction stimulates the hyperphosphorylation of IkappaB-alpha inhibitory protein. Conversely, overexpression of a dominant-negative IkappaB-alpha transgene mutated at S32 and S36 residues, abolishes gp120(env)-induced NF-kappaB activation. IkappaB kinases (IKKs) activity was found to be selectively enhanced following CD4 engagement with gp120(env) and to mediate the phosphorylation of IkappaB-alpha while co-transfection experiments using dominant-negative forms of IKKs inhibited gp120(env)-induced NF-kappaB activation. Taken together, these results confirm that IKKs complex play a key role in gp120(env)-induced NF-kappaB activation.
authors.affiliation: Laboratoire Infections Rétrovirales et Signalisation Cellulaire, CNRS UMR 5121, Institut de Biologie, 4 Bd Henri IV, 34060, Montpellier, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bossis
authors.forename: Sara
authors.initials: S
authors.lastname: Salinas
authors.forename: Christine
authors.initials: C
authors.lastname: Cartier
authors.forename: Christian
authors.initials: C
authors.lastname: Devaux
authors.forename: Laurence
authors.initials: L
authors.lastname: Briant
mesh_terms: D015704:CD4 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D004268:DNA-Binding Proteins / Q000378:metabolism; D017930:Genes, Reporter; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D015704:CD4 Antigens; D004268:DNA-Binding Proteins; D015699:HIV Envelope Protein gp120; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human