NUCLEAR-LOCALIZATION SIGNALS ALSO MEDIATE THE OUTWARD MOVEMENT OF PROTEINS FROM THE NUCLEUS

Several nuclear proteins, including steroid hormone receptors, have be en shown to shuttle continuously between the nucleus and the cytoplasm . The mechanism of entry of proteins into the nucleus is well document ed, whereas the mechanism of their outward movement into the cytoplasm is not understood. We have grafted the nuclear localization signals o f the progesterone receptor or the simian virus 40 large tumor antigen onto beta-galactosidase. These additions were shown to impart to the protein the ability to shuttle between the nucleus and the cytoplasm. Microinjected proteins devoid of a nuclear localization signal were un able to exit from the nucleus. The same nuclear localization signals a re thus involved in both the inward and the outward movement of protei ns through the nuclear membrane. We also show that although the nuclea r import requires energy, the nuclear export does not. These results s uggest that the nucleocytoplasmic shuttling may be a general phenomeno n for nuclear proteins that could possibly undergo modifications in th e cytoplasm and exert some biological activities there. These conclusi ons also imply that at least part of the cellular machinery involved i n the nuclear import of proteins may function bidirectionally.