IκB family members function by different mechanisms

The I kappaB family of proteins regulates NF-kappaB-dependent transcription by inhibiting DNA binding and localizing these factors to the cell cytoplasm, I kappaB alpha does this by shifting the balance between nuclear import of Rel proteins and their export from the nucleus. Here we show that, unlike I kappaB alpha, I kappaB beta and I kappaB beta appear to sequester p65 or c-Rel in the cytoplasm by inhibiting nuclear import. Furthermore, because I kappaB beta does not undergo nucleocytoplasmic shuttling, it cannot remove nuclear proteins like I kappaB alpha does. We conclude that the mechanism of action differs among I kappaB family members.