The NF-kB interaction group was formed in 2005 even before our Program Project Grant was funded. This group website provides a medium for sharing information among the five groups participating in the program. The five research groups are headed by:
Elizabeth Komives
Gourisankar Ghosh
Peter Wolynes
Jane Dyson
Alexander Hoffmann

The overall goals of the project are to explore the dynamics of the interaction between the NF- kB transcription factors and their inhibitors. We are especially interested in making theoretical predictions of whether and where folding is coupled to binding in the interaction, and linking biophysical measurements such as kinetics and thermodynamics with cellular responses. Together we have already discovered a number of interesting aspects of this tightly regulated signaling response. For example, Peter Wolynes' group predicted that the inhibitor IkBa would be partially folded when free in solution. The Komives lab used biophysical measurements to validate this prediction. Gourisankar Ghosh's lab found that IkBa is degraded very quickly by the 20s proteasome, and Alex Hoffmann showed that in cells, the half-life of IkBa is extremely short and it is degraded by a ubiquitin-independent pathway. T he NF- kB/IkB signaling system represents a unique example where a deep biophysical understanding of the protein interaction dynamics can be quantitatively linked to the emergent biological response.