Nuclear localization of IκBα promotes active transport of NF-κB from the nucleus to the cytoplasm

Abstract

IκBα tightly regulates the transcriptional activity of NF-κB by retaining it in the cytoplasm in an inactive form. In the present work, we report that IκBα, when expressed in the nuclear compartment, not only abrogates NF-κB/DNA interactions and NF-κB-dependent transcription, but also transports NF-κB back to the cytoplasm. This function of IκBα is insured by a nuclear export sequence located in the C-terminal domain of IκBα and homologous to the previously described export signal found in HIV-1 Rev protein as well as in PKI (the inhibitor of the catalytic subunit of protein kinase A). Thus, inhibition of NF-κB/DNA binding and the consecutive efficient nuclear export of the transcription factor by IκBα could represent an important mechanism for the control of the expression of NF-κB-dependent genes.