Seminar

Regulation of p100 processing by p105

Gunnar Dittmar, PhD

The non-canonical NF-ɻB pathway relies on processing of the NF- ɻB precursor protein p100. This pathway differs from the canonical NF-ɻB pathway not only in the activators and the downstream signalling mechanisms, but importantly also, in the kinetics of activation. In addition to the well-established upstream regulators of non-canonical NF-ɻB activation, we show for the first time that NF-ɻB precursor p105 regulates the kinetics and efficiency of p100 processing. Mathematical modelling was employed to predict the possible modes of regulatory interactions between p100 and p105 precursors. These models were experimentally verified by precursor interaction studies, and comparative analyses of NF-ɻB activation in response to different stimuli in cells lacking the precursor proteins. Collectively, these results strongly suggest a novel regulatory network of NF-kB activation.