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

Rodrigo Cabrera, Zhe Sha, Tegy J. Vadakkan, Joel Otero, Franziska Kriegenburg, Rasmus Hartmann-Petersen, Mary E. Dickinson, Eric C. Chang

18 Citationer (Scopus)
57 Downloads (Pure)

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.
OriginalsprogEngelsk
TidsskriftMolecular Biology of the Cell
Vol/bind21
Udgave nummer18
Sider (fra-til)3125-3136
Antal sider12
ISSN1059-1524
DOI
StatusUdgivet - 15 sep. 2010

Fingeraftryk

Dyk ned i forskningsemnerne om 'Proteasome nuclear import mediated by Arc3 can influence efficient DNA damage repair and mitosis in Schizosaccharomyces pombe'. Sammen danner de et unikt fingeraftryk.

Citationsformater