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NF‐κB activation upon interaction of HIV‐1 envelope glycoproteins with cell surface CD4 involves IκB kinases
Author(s) -
Bossis Guillaume,
Salinas Sara,
Cartier Christine,
Devaux Christian,
Briant Laurence
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)02566-8
Subject(s) - kinase , microbiology and biotechnology , transcription factor , signal transduction , phosphorylation , intracellular , nf κb , glycoprotein , hyperphosphorylation , chemistry , transfection , biology , biochemistry , gene
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‐κB (NF‐κB) transcription factor. The present work further investigates the signal transduction pathways involved in gp120 env ‐induced NF‐κB activation. We demonstrate that gp120 env –CD4 interaction stimulates the hyperphosphorylation of IκB‐α inhibitory protein. Conversely, overexpression of a dominant‐negative IκB‐α transgene mutated at S32 and S36 residues, abolishes gp120 env ‐induced NF‐κB activation. IκB kinases (IKKs) activity was found to be selectively enhanced following CD4 engagement with gp120 env and to mediate the phosphorylation of IκB‐α while co‐transfection experiments using dominant‐negative forms of IKKs inhibited gp120 env ‐induced NF‐κB activation. Taken together, these results confirm that IKKs complex play a key role in gp120 env ‐induced NF‐κB activation.