IDENTIFICATION OF A SIGNAL FOR RAPID EXPORT OF PROTEINS FROM THE NUCLEUS

Active nuclear import of protein is controlled by nuclear localization signals (NLSs), but nuclear export is not understood well. Nuclear tr afficking of the catalytic (C) subunit of cAMP-dependent protein kinas e (cAPK) is critical for regulation of gene expression. The heat-stabl e inhibitor (PKI) of cAPK contains a nuclear export signal (NES) that triggers rapid, active net extrusion of the C-PKI complex from the nuc leus. This NES (residues 35-49), fused or conjugated to heterologous p roteins, was sufficient for rapid nuclear export. Hydrophobic residues were critical. The NES is a slightly weaker signal than the SV40 NLS. A sequence containing only residues 37-46, LALKLAGLDI, is also suffic ient for nuclear export. This is an example of a protein-based NES hav ing no obvious association with RNA. A similar sequence, LQLPPLERLTL, from Rev, an RNA-binding protein of HIV-1, also is an NES.