Inhibition of transcription factor NF-kappaB activation by kappaB-Ras.
kappaB-Ras1 and kappaB-Ras2 are two small proteins that display similarity at the amino acid level to Ras-like small GTPases. Although little is known about the function of the kappaB-Ras proteins, they have been shown to interfere with activation of transcription factor NF-kappaB. They accomplish this by binding to IkappaB proteins, natural inhibitors of NF-kappaB, and delaying their stimulus-dependent degradation. In this chapter, we consider the kappaB-Ras proteins in light of their NF-kappaB regulatory properties. Three fundamental questions about kappaB-Ras function are addressed: (1) Does kappaB-Ras regulate NF-kappaB in vivo? (2) Does kappaB-Ras selectively regulate specific NF-kappaB/IkappaB complexes? (3) Does kappaB-Ras function as a true GTPase, that is, with molecular switching properties that correlate with the phosphorylation state of bound guanine nucleotide? Finally, we detail the methods currently used to study the kappaB-Ras proteins as regulators of NF-kappaB activation.
Huxford
Tom
T
Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, USA.
Ghosh
Gourisankar
G
D000818:Animals; D006801:Humans; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D018631:ras Proteins / Q000502:physiology*
D020672:I-kappa B Proteins; D016328:NF-kappa B; D018631:ras Proteins