Proteasome nuclear import mediated by Arc3 can influence efficient DNA damage repair and mitosis in Schizosaccharomyces pombe

TY - JOUR

T1 - Proteasome nuclear import mediated by Arc3 can influence efficient DNA damage repair and mitosis in Schizosaccharomyces pombe

AU - Cabrera, Rodrigo

AU - Sha, Zhe

AU - Vadakkan, Tegy J.

AU - Otero, Joel

AU - Kriegenburg, Franziska

AU - Hartmann-Petersen, Rasmus

AU - Dickinson, Mary E.

AU - Chang, Eric C.

PY - 2010/9/15

Y1 - 2010/9/15

N2 - 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.

AB - 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.

KW - Actin-Related Protein 2-3 Complex

KW - Active Transport, Cell Nucleus

KW - Cell Nucleus

KW - DNA Damage

KW - DNA Repair

KW - Fluorescence Recovery After Photobleaching

KW - Humans

KW - Mitosis

KW - Proteasome Endopeptidase Complex

KW - Recombinant Fusion Proteins

KW - Schizosaccharomyces

KW - Schizosaccharomyces pombe Proteins

U2 - 10.1091/mbc.E10-06-0506

DO - 10.1091/mbc.E10-06-0506

M3 - Journal article

C2 - 20668161

SN - 1059-1524

VL - 21

SP - 3125

EP - 3136

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

IS - 18

ER -