Sts1 Plays a Key Role in Targeting Proteasomes to the Nucleus

• Published in: The Journal of biological chemistry 2011-01, Vol.286 (4), p.3104-3118
• Main Authors: Chen, Li, Romero, Lizbeth, Chuang, Show-Mei, Tournier, Vincent, Joshi, Kishore Kumar, Lee, Jung Ah, Kovvali, Gopala, Madura, Kiran
• Format: Article
• Language: English
• Subjects: Active Transport, Cell Nucleus - physiology; Cell Nucleus - genetics; Cell Nucleus - metabolism; Nuclear Localization Signal; Nuclear Localization Signals - genetics; Nuclear Localization Signals - metabolism; Nuclear Translocation; Proteasome Endopeptidase Complex - genetics; Proteasome Endopeptidase Complex - metabolism; Protein Degradation; Protein Synthesis and Degradation; Protein-Protein Interactions; Proteolytic Enzymes; Rad23; Rpn10; Rpn11; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Srp1; Ubiquitin
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M110.135863

The evidence that nuclear proteins can be degraded by cytosolic proteasomes has received considerable experimental support. However, the presence of proteasome subunits in the nucleus also suggests that protein degradation could occur within this organelle. We determined that Sts1 can target proteasomes to the nucleus and facilitate the degradation of a nuclear protein. Specific sts1 mutants showed reduced nuclear proteasomes at the nonpermissive temperature. In contrast, high expression of Sts1 increased the levels of nuclear proteasomes. Sts1 targets proteasomes to the nucleus by interacting with Srp1, a nuclear import factor that binds nuclear localization signals. Deletion of the NLS in Sts1 prevented its interaction with Srp1 and caused proteasome mislocalization. In agreement with this observation, a mutation in Srp1 that weakened its interaction with Sts1 also reduced nuclear targeting of proteasomes. We reported that Sts1 could suppress growth and proteolytic defects of rad23Δ rpn10Δ. We show here that Sts1 suppresses a previously undetected proteasome localization defect in this mutant. Taken together, these findings explain the suppression of rad23Δ rpn10Δ by Sts1 and suggest that the degradation of nuclear substrates requires efficient proteasome localization.