Proteasomal degradation of Bcl-2, inhibition

Azad, N., Vallyathan, V., Wang, L., Tantishaiyakul, V., Stehlik, C., Leonard, S.S., Rojanasakul, Y. (2006). S-nitrosylation of Bcl-2 inhibits its ubiquitin-proteasomal degradation. A novel antiapoptotic mechanism that suppresses apoptosis. J. Biol. Chem. 281(AS), 34124-34134. 

Bcl-2 is a key apoptosis regnlatory protein of the mitochondrial death pathway whose function is dependent on its expression levels. NO prevented Bcl-2 cleavage and suppressed cytochrome c release in TNF-a and actinomycin D-treated adenocarcinoma (MCF-7) cells exposed to SNAP (Kim et al. 1998). This level is regulated by a ubiqutination-proteasome degradation system. There was inhibition of NO production by the NO scavenger. The NO donors DPTA/NONO and sodium nitro-prusside effectively upregulated Bcl-2 S-nitrosylation, decreased its ubiquitination, and inhibited apoptotic cell death induced by chromium. The effect of NO on Bcl-2 stability was shown to be independent of its dephosphorylation (Azad et al. 2006). 

Bcl-2 is a key apoptosis regulatory protein of the mitochondrial death pathway. It is dependent on posttranslational modifications, such as ubiquitination and proteasomal degradation (Dimmeler et al. 1999). NO S-nitrosylates Bcl-2 and inhibits... 

---