title: BubR1 is modified by sumoylation during mitotic progression.
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.
authors.affiliation: Departments of Environmental Medicine and Pharmacology, New York University School of Medicine, Tuxedo, New York 10987, USA.
authors.forename: Feikun
authors.initials: F
authors.lastname: Yang
authors.forename: Liyan
authors.initials: L
authors.lastname: Hu
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.forename: Jianxiu
authors.initials: J
authors.lastname: Yu
authors.forename: Christopher B
authors.initials: CB
authors.lastname: O'Connell
authors.forename: Alexey
authors.initials: A
authors.lastname: Khodjakov
authors.forename: Michele
authors.initials: M
authors.lastname: Pagano
authors.forename: Wei
authors.initials: W
authors.lastname: Dai
mesh_terms: D000107:Acetylation; D019943:Amino Acid Substitution; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D020125:Mutation, Missense; D010766:Phosphorylation / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism; D058207:Sumoylation / Q000502:physiology*
chemical_list: D025842:SUMO-1 Protein; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases