Abstract
Proteasomes are conserved protease complexes enriched in the nuclei of dividing yeast cells, a major site for protein degradation. If yeast cells do not proliferate and transit to quiescence, metabolic changes result in the dissociation of proteasomes into proteolytic core and regulatory complexes and their sequestration into motile cytosolic proteasome storage granuli. These granuli rapidly clear with the resumption of growth, releasing the stored proteasomes, which relocalize back to the nucleus to promote cell cycle progression. Here, I report on three models of how proteasomes are transported from the cytoplasm into the nucleus of yeast cells. The first model applies for dividing yeast and is based on the canonical pathway using classical nuclear localization sequences of proteasomal subcomplexes and the classical import receptor importin/karyopherin αβ. The second model applies for quiescent yeast cells, which resume growth and use Blm10, a HEAT-like repeat protein structurally related to karyopherin β, for nuclear import of proteasome core particles. In the third model, the fully-assembled proteasome is imported into the nucleus. Our still marginal knowledge about proteasome dynamics will inspire the discussion on how protein degradation by proteasomes may be regulated in different cellular compartments of dividing and quiescent eukaryotic cells.
Highlights
Proteasomes are conserved protease complexes enriched in the nuclei of dividing yeast cells, a major site for protein degradation
The finding that cytosolic proteasomes are not indispensable for protein degradation, while nuclear proteasomes are essential in yeast, challenged the concept that proteasomal proteolysis primarily occurs in the cytoplasm [7]
According to the well-established model of nuclear import, the cargo:import receptor complex is assembled in the cytoplasm, where Ran is bound to GDP due to the Ran-GTPase activating enzyme, RanGAP
Summary
The ubiquitin-proteasome system accounts for 80%–90% of the protein breakdown in growing yeast and mammalian cells. A growing body of literature demonstrates that misfolded proteins synthesized in the cytoplasm are trafficked to the nucleus for degradation (for a review, see [5]), nuclear proteins can be exported into the cytoplasm for degradation [6] In this context, the finding that cytosolic proteasomes are not indispensable for protein degradation, while nuclear proteasomes are essential in yeast, challenged the concept that proteasomal proteolysis primarily occurs in the cytoplasm [7]. The finding that cytosolic proteasomes are not indispensable for protein degradation, while nuclear proteasomes are essential in yeast, challenged the concept that proteasomal proteolysis primarily occurs in the cytoplasm [7] It is unknown how cytosolic misfolded proteins are targeted into the nucleus, intriguing results suggest that the canonical nuclear import pathway couples ribosome-bound nascent polypeptides to proteasomes for degradation in yeast [8]. To elucidate the major sites of proteasomal protein degradation, it is important understand the dynamics of proteasomes between the nucleus and the cytoplasm
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