Ras Proteins and IκB Degradation

Abstract

The IκB proteins are inhibitors of the NF-κB transcription factor, which has major functions in gene regulation in response to inflammatory stimuli of the immune system. In this system, transcription is controlled though regulated proteolysis of the IκB inhibitory proteins. In screening proteins that interact with IκB, Fenwick et al . detected a protein they call κB-Ras1 because of its similarity to the small guanosine triphosphatase Ras. The κB-Ras1 protein is unusual in that it has mutations similar to those found in oncogenic mutants of Ras. The κB-Ras1 and IκB proteins were shown to interact in intact cells. Overexpression of κB-Ras1 decreased degradation of IκB proteins in cells and consequently decreased NF-κB-dependent transcription. The κB-Ras1 protein appears to associate specifically with complexes of NF-κB with IκBβ, which may explain why IκBβ is degraded more slowly than is IκBα. Fenwick, C., Na, S.-Y., Voll, R.E., Zhong, H., Im, S.-Y., Lee, J.W., and Ghosh, S. (2000) A subclass of Ras proteins that regulate the degradation of IκB. Science 287: 869-873. [Abstract] [Full Text]