Bcl3 and REG-gamma are the Regulators of NF-kappaB p50 and p52
Apart from the canonical and non-canonical activation pathway of NF-κB, the atypical IκB family member Bcl3, can regulate p50 and p52 homodimers’ activity. These dimers, known for their transcriptional repression, switch to activate tran-scription by associating with Bcl3. Several prior studies showed that transcriptional activity of Bcl3 requires extensive phosphorylation.
In this study, I confirmed the significance of three phosphorylation sites of Bcl3, Ser33, 114 and 446 by using kinase knockdown cells and kinase-specific inhibitors. AKT, ERK2 and IKK phosphorylate these sites respectively. In addition, I also identi-fied a new site of Bcl3, Ser366. My experiments suggest that both AKT and ERK2 are potential kinases targeting this site.
I have also showed that p50 generation can be regulated by a proteasome reg-ulator. This regulator maintains low level of free p50 in the nucleus and proper levels of gene expression at basal levels. Future experiments will determine if p52 generation is also regulated by these proteasome regulators.