NF‐κB activation upon interaction of HIV‐1 envelope glycoproteins with cell surface CD4 involves IκB kinases

FEBS Letters

Cartier, Christine¹  Devaux, Christian¹  Briant, Laurence¹  Salinas, Sara¹  Bossis, Guillaume¹ 

[1] Laboratoire Infections Rétrovirales et Signalisation Cellulaire, CNRS UMR 5121, Institut de Biologie, 4 Bd Henri IV, 34060 Montpellier, France

关键词: Human immunodeficiency virus type-1;    CD4;    IκB kinase;    Nuclear factor-κB;    IκB;    IKK;    IκB kinase;    WT;    wild type;    DN;    dominant negative;    LTR;    long terminal repeat;   

DOI  :  10.1016/S0014-5793(02)02566-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown