Nuclear targeting of proteins: how many different signals?

The nuclear import of proteins into the cell nucleus involves the recogniti on of a nuclear localization signal sequence, borne by the protein to be tr ansported, by complex molecules called importins, that will subsequently me diate the crossing over of the nuclear envelope. The most frequently encoun tered signal sequence is made up of short stretches of basic amino acid res idues and is recognized by importins alpha and/or beta. Other signal sequen ces have been described, and some have been shown to mediate the associatio n with importins other than importin alpha or beta. Recently, approaches ha ve been developed that allow the cloning, on a functional basis, of sequenc es able to specify the nuclear localization of proteins. A variety of pepti dic motifs of limited size which do not contain previously described signal sequences were isolated in such assays. It reveals that the spectrum of se quences that are able to target a protein to the cell nucleus may be wider than currently expected. It will probably also lead to the identification o f novel target sequences for importins and will demonstrate the implication of additional members of this family of proteins in nuclear transport. (C) 2000 Elsevier Science Inc. All rights reserved.