The I kappaB family of proteins regulates NF-kappaB-dependent transcription
by inhibiting DNA binding and localizing these factors to the cell cytopla
sm, 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, unli
ke 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, becaus
e I kappaB beta does not undergo nucleocytoplasmic shuttling, it cannot rem
ove nuclear proteins like I kappaB alpha does. We conclude that the mechani
sm of action differs among I kappaB family members.