Oxidative, multistep activation of the noncanonical NF-κB pathway via disulfide Bcl-3/p50 complex

被引:25
作者
Cristofanon, Silvia [1 ,2 ]
Morceau, Franck [2 ]
Scovassi, A. Ivana [3 ]
Dicato, Mario [2 ]
Ghibelli, Lina [1 ]
Diederich, Marc [2 ]
机构
[1] Univ Roma Tor Vergata, Dipartimento Biol, I-00133 Rome, Italy
[2] Hop Kirchberg, Lab Biol Mol & Ecllulaire Canc, Fdn Rech Canc & Maladies Sang, L-2540 Luxembourg, Luxembourg
[3] Ist Genet Mol Consiglio Nazl Ric, Pavia, Italy
关键词
glutathione; Bcl-2; ROS; p38; GLUTATHIONE DEPLETION; MAP KINASE; NUCLEAR TRANSLOCATION; BCL-2; EXPRESSION; P50; HOMODIMERS; CELLS; APOPTOSIS; TRANSCRIPTION; BINDING; MODULATION;
D O I
10.1096/fj.07-104109
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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)
引用
收藏
页码:45 / 57
页数:13
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