Proteasome nuclear import mediated by Arc3 can influence efficient DNA damage repair and mitosis in Schizosaccharomyces pombe
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Proteasome nuclear import mediated by Arc3 can influence efficient DNA damage repair and mitosis in Schizosaccharomyces pombe. / Cabrera, Rodrigo; Sha, Zhe; Vadakkan, Tegy J.; Otero, Joel; Kriegenburg, Franziska; Hartmann-Petersen, Rasmus; Dickinson, Mary E.; Chang, Eric C.
I: Molecular Biology of the Cell, Bind 21, Nr. 18, 2010, s. 3125-3136.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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
Y1 - 2010
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
VL - 21
SP - 3125
EP - 3136
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
SN - 1059-1524
IS - 18
ER -
ID: 33892510