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Spindle pole fragmentation due to proteasome inhibition
Anka G Ehrhardt1, Greenfield Sluder
1Department of Cell Biology, University of Massachusetts Medical School, Worcester, 01605, USA. anka.ehrhardt@umassmed.edu
Journal of Cellular Physiology
|April 14, 2005
Summary
The centrosome acts as a proteolytic center during mitosis, maintaining spindle pole integrity. Proteasome inhibition causes excessive protein buildup, leading to supernumerary asters and spindle pole fragmentation.
Area of Science:
- Cell Biology
- Molecular Biology
Background:
- Centrosomes concentrate proteasomes during interphase, forming a proteolytic center.
- The centrosome's role as a proteolytic center during mitosis remains uncharacterized.
Purpose of the Study:
- To investigate whether centrosomes function as proteolytic centers during mitosis.
- To understand the mechanisms behind spindle pole integrity maintenance.
Main Methods:
- Cultured mammalian cells were treated with the proteasome inhibitor MG 132.
- Spindle morphology in mitotic cells was analyzed.
- Microtubule-based transport and protein synthesis were inhibited.
Main Results:
- Proteasome inhibition during mitosis induced supernumerary asters and multipolar spindles.
- Inhibiting microtubule transport or protein synthesis prevented aster formation.
- Expression of dsRed without proteasome inhibition caused spindle pole fragmentation.
Conclusions:
- Centrosomes function as proteolytic centers during mitosis.
- Proteolytic activity at spindle poles is crucial for maintaining spindle pole integrity.
- Excessive protein accumulation at spindle poles, due to proteasome inhibition, leads to centrosome fragmentation.