A distinctive physiological role for I kappa B beta in the propagation of mitochondrial respiratory stress signaling

作者：Biswas Gopa; Tang Weigang; Sondheimer Neal; Guha Manti; Bansal Seema; Avadhani Narayan G^*

来源：Journal of Biological Chemistry, 2008, 283(18): 12586-12594.

DOI：10.1074/jbc.M710481200

The NF kappa Bs regulate an array of physiological and pathological processes, including propagation of mitochondrial respiratory stress signaling in mammalian cells. We showed previously that mitochondrial stress activates NF kappa B using a novel calcineurin-requiring pathway that is different from canonical or non-canonical pathways. This study shows that I kappa B beta is essential for the propagation of mitochondrial stress signaling. Knock down of I kappa B beta, but not I kappa B alpha, mRNA reduced the mitochondrial stress-mediated activation and nuclear translocation of cRel:p50, inhibiting expression of nuclear target genes RyR1 and cathepsin L. I kappa B beta mRNA knock down also reduced resistance to staurosporine-induced apoptosis and decreased in vitro invasiveness. Induced receptor switching to insulin-like growth factor-1 receptor and increased glucose uptake are hallmarks of mitochondrial stress. I kappa B beta mRNA knock down selectively abrogated the receptor switch and altered tubulin cytoskeletal organization. These results show that mitochondrial stress signaling uses an I kappa B beta-initiated NF kappa B pathway that is distinct from the other known NF kappa B pathways. Furthermore, our results demonstrate the distinctive physiological roles of the two inhibitory proteins I kappa B beta and I kappa B alpha

• 出版日期2008-5-2