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

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3125-3136
Number of pages12
JournalMolecular Biology of the Cell
Volume21
Issue number18
DOIs
StatePublished - Sep 15 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Medicine

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