Aurora B hyperactivation by Bub1 overexpression promotes chromosome missegregation.
High expression of the mitotic kinase Bub1 is associated with a variety of human cancers and correlates with poor clinical prognosis, but whether Bub1 alone can drive tumorigenesis was unknown. We provided conclusive evidence that Bub1 has oncogenic properties by generating transgenic mice that overexpress Bub1 in a wide variety of tissues, resulting in aneuploidization. Consistently, Bub1 transgenic mice developed various kinds of spontaneous tumors as well as accelerated Myc-induced lymphomagenesis. While the mitotic checkpoint was robust in Bub1 overexpressing cells, misaligned and lagging chromosomes were observed. These defects originated from increased Aurora B activity and could be suppressed by inhibition of Aurora B. Taken together, this indicates that Bub1 has oncogenic properties and imply that aneuploidization and tumorigenesis result from Aurora B-dependent missegregation. Here, we focus on the complex relationship between Bub1 and Aurora B and discuss the broader implications of Bub1-dependent Aurora B activation in mediating error correction.
Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA.
Robin M
RM
Ricke
Jan M
JM
van Deursen
D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D020090:Chromosome Segregation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008954:Models, Biological; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology
C576921:AURKB protein, human; C576924:Aurkb protein, mouse; D064107:Aurora Kinase B; D064127:Aurora Kinases; C584277:BUB1 protein, human; C584281:Bub1 protein, mouse; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases