Journal
FASEB JOURNAL
Volume 23, Issue 1, Pages 45-57Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.07-104109
Keywords
glutathione; Bcl-2; ROS; p38
Categories
Funding
- Bourse de Formation-Recherche of the Ministere de la Culture
- de l'Enseignement superieur et de la Recherche of Luxembourg
- Televie
- Fondation de Recherche Cancer et Sang
- Recherches Scientifiques Luxembourg association
- Een Haerz fir Kriibskrank Kanner association
- Action Lions Vaincre le Cancer
- Fonds National de la Recherche-Luxembourg
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Buthionine sulfoximine ( BSO) is a well-known inhibitor of glutathione synthesis, producing slow glutathione ( GSH) depletion and oxidative stress; some responder cells avoid BSO-induced death by trans-activating the prosurvival protein Bcl-2. Here we show that BSO activates a noncanonical, inhibitory NF-kappa B- and p65-independent NF-kappa B pathway via a multistep process leading to the up-regulation of Bcl-2. The slow BSO-induced GSH depletion allows separation of two redox-related phases, namely, early thiol disequilibrium and late frank oxidative stress; each phase contributes to the progressive activation of a p50-p50 homodimer. The early phase, coinciding with substantial thiol depletion, produces a cytosolic preparative complex, consisting of p50 and its interactor Bcl-3 linked by interprotein disulfide bridges. The late phase, coinciding with reactive oxygen species production, is responsible, probably via p38 activation, for nuclear targeting of the complex and trans-activation of Bcl-2. Cristofanon, S., Morceau, F., Scovassi, A. I., Dicato, M., Ghibelli, L., Diederich, M. Oxidative, multistep activation of the noncanonical NF-kappa B pathway via disulfide Bcl-3/p50 complex. FASEB J. 23, 45-57 ( 2009)
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