Sluder Lab Publications


Spindle pole fragmentation due to proteasome inhibition

UMMS Affiliation

Department of Cell Biology

Publication Date


Document Type



Animals; Antigens, Nuclear; Biological Transport; Cell Line; Centrosome; Cricetinae; Dyneins; Humans; Interphase; Leupeptins; Mice; Microtubules; Mitosis; Mitotic Spindle Apparatus; Nuclear Matrix-Associated Proteins; Nuclear Proteins; Proteasome Endopeptidase Complex; Protein Binding; Transcription, Genetic; Tubulin; Ubiquitin


Cell Biology


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.

DOI of Published Version



J Cell Physiol. 2005 Sep;204(3):808-18. Link to article on publisher's site

Journal/Book/Conference Title

Journal of cellular physiology

Related Resources

Link to Article in PubMed

PubMed ID