Transcriptional Regulation
Ras Proteins and I
B Degradation
The I
B proteins are inhibitors of the NF-
B 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 I
B inhibitory proteins. In screening proteins that interact with I
B, Fenwick et al. detected a protein they call
B-Ras1 because of its similarity to the small guanosine triphosphatase Ras. The
B-Ras1 protein is unusual in that it has mutations similar to those found in oncogenic mutants of Ras. The
B-Ras1 and I
B proteins were shown to interact in intact cells. Overexpression of
B-Ras1 decreased degradation of I
B proteins in cells and consequently decreased NF-
B-dependent transcription. The
B-Ras1 protein appears to associate specifically with complexes of NF-
B with I
Bβ, which may explain why I
Bβ is degraded more slowly than is I
Bα.
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 I
B. Science 287: 869-873. [Abstract] [Full Text]