Yeast importin-α (Srp1) performs distinct roles in the import of nuclear proteins and in targeting proteasomes to the nucleus.

Srp1 (importin-α) can translocate proteins that contain a nuclear localization signal (NLS) into the nucleus. The loss of Srp1 is lethal, although several temperature-sensitive mutants have been described. Among these mutants, srp1-31 displays the characteristic nuclear import defect of importin-α mutants, whereas srp1-49 shows a defect in protein degradation. We ...
characterized these and additional srp1 mutants to determine whether distinct mechanisms were required for intracellular proteolysis and the import of NLS-containing proteins. We determined that srp1 mutants that failed to import NLS-containing proteins (srp1-31 and srp1-55) successfully localized proteasomes to the nucleus. In contrast, srp1 mutants that did not target proteasomes to the nucleus (srp1-49 and srp1-E402Q) were able to import NLS-containing proteins. The proteasome targeting defect of specific srp1 mutants caused stabilization of nuclear substrates and overall accumulation of multiubiquitylated proteins. Co-expression of a member of each class of srp1 mutants corrected both the proteasome localization defect and the import of NLS-containing proteins. These findings indicate that the targeting of proteasomes to the nucleus occurs by a mechanism distinct from the Srp1-mediated import of nuclear proteins.
Mesh Terms:
Active Transport, Cell Nucleus, Alleles, Cell Nucleus, Cytosol, Genetic Complementation Test, Green Fluorescent Proteins, Karyopherins, Microscopy, Fluorescence, Mutation, Nuclear Localization Signals, Nuclear Proteins, Plasmids, Proteasome Endopeptidase Complex, Protein Structure, Tertiary, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Temperature, Ubiquitin
J. Biol. Chem.
Date: Nov. 14, 2014
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