NUCLEAR-LOCALIZATION OF I-KAPPA-B-ALPHA PROMOTES ACTIVE-TRANSPORT OF NF-KAPPA-B FROM THE NUCLEUS TO THE CYTOPLASM

I kappa B alpha tightly regulates the transcriptional activity of NF-k appa B by retaining it in the cytoplasm in an inactive form. In the pr esent work, we report that I kappa B alpha, when expressed in the nucl ear compartment, not only abrogates NF-kappa B/DNA interactions and NF -kappa B-dependent transcription, but also transports NF-kappa B back to the cytoplasm. This function of I kappa B alpha is insured by a nuc lear export sequence located in the C-terminal domain of I kappa B alp ha and homologous to the previously described export signal found in H IV-1 Rev protein as well as in PKI (the inhibitor of the catalytic sub mit of protein kinase A). Thus, inhibition of NF-kappa B/DNA binding a nd the consecutive efficient nuclear export of the transcription facto r by I kappa B alpha could represent an important mechanism for the co ntrol of the expression of NF-kappa B-dependent genes.