Spindle pole fragmentation due to proteasome inhibition.

Abstract:

:During interphase, the centrosome concentrates cell stress response molecules, including chaperones and proteasomes, into a proteolytic center. However, whether the centrosome functions as proteolytic center during mitosis is not known. In this study, cultured mammalian cells were treated with the proteasome inhibitor MG 132 and spindle morphology in mitotic cells was characterized in order to address this issue. Proteasome inhibition during mitosis leads to the formation of additional asters that cause the assembly of multipolar spindles. The cause of this phenomenon was investigated by inhibiting microtubule-based transport and protein synthesis. These experimental conditions prevented the formation of supernumerary asters during mitosis. In addition, the expression of dsRed without proteasome inhibition led to the fragmentation of spindle poles. These experiments showed that the formation of extra asters depends on intact microtubule-based transport and protein synthesis. These results suggest that formation of supernumerary asters is due to excessive accumulation of proteins at the spindle poles and consequently fragmentation of the centrosome. Together, this leads to the conclusion that the centrosome functions as proteolytic center during mitosis and proteolytic activity at the spindle poles is necessary for maintaining spindle pole integrity.

journal_name

J Cell Physiol

authors

Ehrhardt AG,Sluder G

doi

10.1002/jcp.20335

keywords:

subject

Has Abstract

pub_date

2005-09-01 00:00:00

pages

808-18

issue

3

eissn

0021-9541

issn

1097-4652

journal_volume

204

pub_type

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