title: Proteasome nuclear import mediated by Arc3 can influence efficient DNA damage repair and mitosis in Schizosaccharomyces pombe.
abstract: Proteasomes must remove regulatory molecules and abnormal proteins throughout the cell, but how proteasomes can do so efficiently remains unclear. We have isolated a subunit of the Arp2/3 complex, Arc3, which binds proteasomes. When overexpressed, Arc3 rescues phenotypes associated with proteasome deficiencies; when its expression is repressed, proteasome deficiencies intensify. Arp2/3 is best known for regulating membrane dynamics and vesicular transport; thus, we performed photobleaching experiments and showed that proteasomes are readily imported into the nucleus but exit the nucleus slowly. Proteasome nuclear import is reduced when Arc3 is inactivated, leading to hypersensitivity to DNA damage and inefficient cyclin-B degradation, two events occurring in the nucleus. These data suggest that proteasomes display Arc3-dependent mobility in the cell, and mobile proteasomes can efficiently access substrates throughout the cell, allowing them to effectively regulate cell-compartment-specific activities.
authors.affiliation: Department of Molecular and Cellular Biology, Interdepartmental Program of Cell and Molecular Biology, and Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Cabrera
authors.forename: Zhe
authors.initials: Z
authors.lastname: Sha
authors.forename: Tegy J
authors.initials: TJ
authors.lastname: Vadakkan
authors.forename: Joel
authors.initials: J
authors.lastname: Otero
authors.forename: Franziska
authors.initials: F
authors.lastname: Kriegenburg
authors.forename: Rasmus
authors.initials: R
authors.lastname: Hartmann-Petersen
authors.forename: Mary E
authors.initials: ME
authors.lastname: Dickinson
authors.forename: Eric C
authors.initials: EC
authors.lastname: Chang
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism*; D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D036681:Fluorescence Recovery After Photobleaching; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D011993:Recombinant Fusion Proteins; D029702:Schizosaccharomyces pombe Proteins; D046988:Proteasome Endopeptidase Complex