The NF-kB family of transcription factors plays a pivotal role in the regulating of inflammation and the development of the immune system. Abnormal alteration of the NF-kB pathway has been implicated in cancer, dysfunction of the immune system, and perhaps aging. Recent evidence has shown that the post-translational modification of the NF-kB members is involved in the activation of this pathway. The mechanism involved in the selective recruitment of the NF-kB members to the numerous possible NF-kB-responsive genes is not been fully elucidated. We are interested in understanding the role of protein phosphorylation in the activation of transcription and the selectivity of gene expression. We have recently demonstrated that the phosphorylation of p65 at serine 536 renders the regulation of this protein independent of the inhibitor IkB. Furthermore, the phosphorylated p65 was differentially recruited to selective promoters following cell activation. These findings suggested that the phosphorylation of p65 at serine 536 might be involved in directing p65 to selective genes. We are currently investigating the role of the various phosphorylation sites on p65 in influencing the specificity of NF-kB-mediated gene expression.
| Sasaki, Carl Y; Slemenda, Colin F; Ghosh, Paritosh et al. (2007) Traf1 induction and protection from tumor necrosis factor by nuclear factor-kappaB p65 is independent of serine 536 phosphorylation. Cancer Res 67:11218-25 |
| Sasaki, Carl Y; Barberi, Theresa J; Ghosh, Paritosh et al. (2005) Phosphorylation of RelA/p65 on serine 536 defines an I{kappa}B{alpha}-independent NF-{kappa}B pathway. J Biol Chem 280:34538-47 |
