I kappa B alpha controls the transcriptional activity of nuclear factor (NF
)-kappa B by retaining it in the cytoplasm; but, when expressed in the nucl
eus, it can also inhibit the interaction of NF-kappa B with DNA and promote
the export of NF-kappa B from the nucleus to the cytoplasm, Here, we repor
t that I kappa B alpha, when not bound to NF-kappa B, is constitutively tra
nsported to the nucleus, and we confirm that the interaction of NF-kappa B
with NF-kappa B retains I kappa B alpha in the cytoplasm, Nuclear import of
I kappa B alpha does not result from passive diffusion but from a specific
energy-dependent transport process that requires the ankyrin repeats of I
kappa B alpha. Nuclear accumulation of I kappa B alpha is dependent on impo
rtins alpha and beta as well as the small GTPase Ran, which are also respon
sible for the nuclear import mediated by basic nuclear localization sequenc
es (NLS). However, these proteins are not sufficient to promote I kappa B a
lpha nuclear translocation. Factor(s) can be removed selectively from cell
extracts with ankyrin repeats of I kappa B alpha which strongly reduce impo
rt of I kappa B alpha but not of proteins containing basic NLS. These findi
ngs indicate that I kappa B alpha is imported in the nucleus by a piggy-bac
k mechanism that involves additional protein(s) containing a basic NLS and
able to interact with ankyrin repeats of I kappa B alpha.