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FEBS Lett. 2002 Apr 10;516(1-3):257-64.

NF-kappaB activation upon interaction of HIV-1 envelope glycoproteins with cell surface CD4 involves IkappaB kinases.

Author information

1
Laboratoire Infections R├ętrovirales et Signalisation Cellulaire, CNRS UMR 5121, Institut de Biologie, 4 Bd Henri IV, 34060, Montpellier, France.

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.

PMID:
11959143
DOI:
10.1016/s0014-5793(02)02566-8
[Indexed for MEDLINE]
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