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 trafficking of the catalytic (C) subunit of cAMP-dependent protein kinase (cAPK) is critical for regulation of gene expression. The heat-stable inhibitor (PKl) of cAPK contains a nuclear export signal (NES) that triggers rapid, active net extrusion of the C-PKl complex from the nucleus. This NES (residues 35-49), fused or conjugated to heterologous proteins, 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 sufficient for nuclear export. This is an example of a protein-based NES having no obvious association with RNA. A similar sequence, LQLPPLERLTL, from Rev, an RNA-binding protein of HIV-1, also is an NES.
Wen
W
W
Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of California, San Diego, La Jolla 92093-0654, USA.
Meinkoth
J L
JL
Tsien
R Y
RY
Taylor
S S
SS
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D047428:Protein Kinase Inhibitors; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D047428:Protein Kinase Inhibitors; D011993:Recombinant Fusion Proteins; D017868:Cyclic AMP-Dependent Protein Kinases