A Highlights from MBoC Selection: Proteasome Nuclear Import Mediated by Arc3 Can Influence Efficient DNA Damage Repair and Mitosis in Schizosaccharomyces Pombe |
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| Authors: | Rodrigo Cabrera Zhe Sha Tegy J. Vadakkan Joel Otero Franziska Kriegenburg Rasmus Hartmann-Petersen Mary E. Dickinson Eric C. Chang |
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| Affiliation: | *Department of Molecular and Cellular Biology, ;§Department of Molecular Physiology and Biophysics, ;‖Interdepartmental Program of Cell and Molecular Biology, and ;†Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030; and ;¶Department of Biology, Section for Biomolecular Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark |
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| 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. |
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