BubR1 is modified by sumoylation during mitotic progression |
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Authors: | Yang Feikun Hu Liyan Chen Cheng Yu Jianxiu O'Connell Christopher B Khodjakov Alexey Pagano Michele Dai Wei |
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Affiliation: | Departments of Environmental Medicine and Pharmacology, New York University School of Medicine, Tuxedo, New York 10987, USA. |
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Abstract: | BubR1 functions as a crucial component that monitors proper chromosome congression and mitotic timing during cell division. We investigated molecular regulation of BubR1 and found that BubR1 was modified by an unknown post-translation mechanism during the cell cycle, resulting in a significant mobility shift on denaturing gels. We termed it BubR1-M as the nature of modification was not characterized. Extended (>24 h) treatment of HeLa cells with a microtubule disrupting agent including nocodazole and taxol or release of mitotic shake-off cells into fresh medium induced BubR1-M. BubR1-M was derived from neither phosphorylation nor acetylation. Ectopic expression coupled with pulling down analyses showed that BubR1-M was derived from SUMO modification. Mutation analysis revealed that lysine 250 was a crucial site for sumoylation. Significantly, compared with the wild-type control, ectopic expression of a sumoylation-deficient mutant of BubR1 induced chromosomal missegregation and mitotic delay. Combined, our study identifies a new type of post-translational modification that is essential for BubR1 function during mitosis. |
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Keywords: | Cell Cycle Checkpoint Control Chromosomes Mitosis Sumoylation Kinetochore Post-translational Modification |
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