title: Sts1 plays a key role in targeting proteasomes to the nucleus.
abstract: 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.
authors.affiliation: Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Lizbeth
authors.initials: L
authors.lastname: Romero
authors.forename: Show-Mei
authors.initials: SM
authors.lastname: Chuang
authors.forename: Vincent
authors.initials: V
authors.lastname: Tournier
authors.forename: Kishore Kumar
authors.initials: KK
authors.lastname: Joshi
authors.forename: Jung Ah
authors.initials: JA
authors.lastname: Lee
authors.forename: Gopala
authors.initials: G
authors.lastname: Kovvali
authors.forename: Kiran
authors.initials: K
authors.lastname: Madura
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019913:Nuclear Localization Signals; C085810:STS1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D046988:Proteasome Endopeptidase Complex