Fiche publication


Date publication

avril 2012

Journal

Cell death & disease

Auteurs

Membres identifiés du Cancéropôle Est :
Pr HERBEIN Georges , Pr ROHR Olivier


Tous les auteurs :
Abbas W, Khan KA, Tripathy MK, Dichamp I, Keita M, Rohr O, Herbein G

Résumé

HIV-1 Nef protein has key roles at almost all stages of the viral life cycle. We assessed the role of the Nef/eEF1A (eukaryotic translation elongation factor 1-alpha) complex in nucleocytoplasmic shuttling in primary human macrophages. Nuclear retention experiments and inhibition of the exportin-t (Exp-t) pathway suggested that cytoplasmic relocalization of eEF1A, mediated by Exp-t, occurs in Nef-treated monocyte-derived macrophages (MDMs). We observed the presence of tRNA in the Nef/eEF1A complexes. Nucleocytoplasmic relocalization of the Nef/eEF1A complexes prevented stress-induced apoptosis of MDMs treated with brefeldin-A. Blockade of stress-induced apoptosis of MDMs treated with HIV-1 Nef resulted from enhanced nucleocytoplasmic transport of eEF1A with decreased release of mitochondrial cytochrome c, and from increased tRNA binding to cytochrome c, ultimately leading to an inhibition of caspase activation. Our results indicate that HIV-1 Nef, through the nucleocytoplasmic relocalization of eEF1A and tRNAs, enhances resistance to stress-induced apoptosis in primary human macrophages.

Mots clés

Active Transport, Cell Nucleus, Apoptosis, drug effects, Brefeldin A, pharmacology, Caspase 3, metabolism, Caspase 9, metabolism, Cells, Cultured, Cytochromes c, metabolism, Endoplasmic Reticulum Stress, drug effects, HIV-1, metabolism, Humans, Macrophages, cytology, Mitochondria, metabolism, Nucleocytoplasmic Transport Proteins, antagonists & inhibitors, Peptide Elongation Factor 1, metabolism, Protein Binding, Protein Interaction Mapping, RNA Interference, RNA, Small Interfering, metabolism, RNA, Transfer, metabolism, Recombinant Proteins, genetics, nef Gene Products, Human Immunodeficiency Virus, genetics

Référence

Cell Death Dis. 2012 Apr;3:e292