Buthionine Sulfoximine (BSO) is a well-known inhibitor of glutathione synthesis, producing slow glutathione depletion and oxidative stress; some “responder” cells avoid BSO-induced death by trans-activating the pro-survival protein Bcl-2. Here we show that BSO activates a non-canonical, IκB- and p65-independent NFκB pathway, via a multi-step process leading to the up-regulation of Bcl-2. The slow BSO-induced GSH depletion allows separating two redox-related phases, namely, early thiol disequilibrium, and late frank oxidative stress; each phase contributes to the progressive activation of a p50-p50 homo-dimer. The early phase, coinciding with substantial thiol depletion, produces a cytosolic preparative complex, consisting of p50 and its inter-actor Bcl-3 linked by inter-protein disulfide bridges. The late phase, coinciding with ROS production, is responsible, probably via p38 activation, of nuclear targeting of the complex, and trans-activation of Bcl-2.
Cristofanon, S. (2008). Pathways of survival to oxidative stress: competition between Bcl-2 and Bax and role of NF-kappaB.
|Titolo:||Pathways of survival to oxidative stress: competition between Bcl-2 and Bax and role of NF-kappaB|
|Data di pubblicazione:||26-ago-2008|
|Anno Accademico:||A.A. 2007/2008|
|Corso di dottorato:||Biologia molecolare e cellulare|
|Settore Scientifico Disciplinare:||Settore BIO/11|
|Tipologia:||Tesi di dottorato|
|Citazione:||Cristofanon, S. (2008). Pathways of survival to oxidative stress: competition between Bcl-2 and Bax and role of NF-kappaB.|
|Appare nelle tipologie:||07 - Tesi di dottorato|