title: Sumoylated BubR1 plays an important role in chromosome segregation and mitotic timing.
abstract: BubR1 is an important component of the spindle assembly checkpoint, and deregulated BubR1 functions frequently result in chromosomal instability and malignant transformation. We recently demonstrated that BubR1 was modified by sumoylation, and that lysine 250 (K250) functions as the crucial site for this modification. BubR1 sumoylation was neither required for its activation nor for binding to kinetochores. However, ectopically expressed sumoylation-deficient BubR1 mutants were retained on the kintochores even after apparent chromosome congression. The kinetochore retention of the sumoylation-deficient mutant of BubR1 caused an anaphase delay coupled with premature sister chromatid separation. Moreover, BubR1 interacted with unphosphorylated Sgo1, and its sumoylation facilitated the interaction. BubR1 sumoylation was inversely associated with its acetylation during mitotic progression. Trichostatin A, a protein deacetylase inhibitor, significantly compromised BubR1 sumoylation. Combined, these results reveal that BubR1 sumoylation plays an important role in its timely removal from the kinetochores and the checkpoint inactivation, thus allowing normal anaphase entry and chromosome segregation.
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY, USA.
authors.forename: Feikun
authors.initials: F
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Dai
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002503:Centromere / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D059566:M Phase Cell Cycle Checkpoints / Q000235:genetics / Q000502:physiology; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation
chemical_list: D018797:Cell Cycle Proteins; C496644:SGO1 protein, human; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases