Proteasomes must efficiently remove their substrates throughout the cells in a timely manner as many of these proteins can be toxic. This study shows that proteasomes can do so efficiently because they are highly mobile. Furthermore this study uncovers that proteasome mobility requires functional Arc3, a subunit of the Arp2/3 complex

Asano K.

Balasubramanian M. K.

Basi G.

Beinhauer J. D.

Bingol B.

Brazer S. C.

Bähler J.

Chen C. R.

Chondrogianni N.

Collins G. A.

Dantuma N. P.

Dubois T.

Elkabetz Y.

Eric C. Chang

Fomproix N.

Forsburg S. L.

Franziska Kriegenburg

Goley E. D.

Gorbea C.

Gordon C.

Gregan J.

Guerrero C.

Higgs H. N.

Ho Y.

Janke C.

Joel Otero

Kearsey S. E.

Kominami K.

Krogan N. J.

Lee W. L.

Marchetti A.

Martin-Garcia R.

Mary E. Dickinson

McCollum D.

Norbury C.

Onken B.

Philimonenko V. V.

Rasmus Hartmann-Petersen

Reits E. A.

Rodrigo Cabrera

Rustici G.

Sap J.

Sato M.

Sha Z.

Stamnes M.

Tatebe H.

Tegy J. Vadakkan

Tran P. T.

Voges D.

Wegner A. M.

Welch M. D.

Wilkinson C. R.

Wilkinson K. D.

William P. Tansey

Woods A.

Wu J. Q.

Yan C.

Yen H. C.

Yen H.-c.S.

Yoshida M.

Zhe Sha

English

PubMed

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.</jats:p

Crossref

Molecular Biology of the Cell

Proteasome Nuclear Import Mediated by Arc3 Can Influence Efficient DNA Damage Repair and Mitosis in Schizosaccharomyces Pombe

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

Cabrera, Rodrigo

Sha, Zhe

Vadakkan, Tegy J.

Otero, Joel

Kriegenburg, Franziska

Hartmann-Petersen, Rasmus

Dickinson, Mary E.

Chang, Eric C.

Copenhagen University Research Information System

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

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https://curis.ku.dk/portal/files/164595396/Cabrera_2010_Proteasone_nuclear.pdf

Proteasome Nuclear Import Mediated by Arc3 Can Influence Efficient DNA Damage Repair and Mitosis in Schizosaccharomyces Pombe

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