A Subclass of Ras Proteins That Regulate the Degradation of IκB

Abstract

Small guanosine triphosphatases, typified by the mammalian Ras proteins, play major roles in the regulation of numerous cellular pathways. A subclass of evolutionarily conserved Ras-like proteins was identified, members of which differ from other Ras proteins in containing amino acids at positions 12 and 61 that are similar to those present in the oncogenic forms of Ras. These proteins, κB-Ras1 and κB-Ras2, interact with the PEST domains of IκBα and IκBβ [inhibitors of the transcription factor nuclear factor kappa B (NF-κB)] and decrease their rate of degradation. In cells, κB-Ras proteins are associated only with NF-κB:IκBβ complexes and therefore may provide an explanation for the slower rate of degradation of IκBβ compared with IκBα.