Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA.
Cell Cycle. 2011 Nov 1;10(21):3645-51. doi: 10.4161/cc.10.21.18156.
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.
高表达有丝分裂激酶 Bub1 与多种人类癌症相关，并与不良的临床预后相关，但 Bub1 是否能单独驱动肿瘤发生尚不清楚。我们通过生成在多种组织中过表达 Bub1 的转基因小鼠提供了确凿的证据，证明 Bub1 具有致癌特性，导致非整倍体。一致地，Bub1 转基因小鼠发展出各种自发肿瘤以及加速 Myc 诱导的淋巴瘤发生。虽然有丝分裂检查点在过表达 Bub1 的细胞中是强大的，但观察到染色体错位和滞后。这些缺陷源于 Aurora B 活性的增加，并且可以通过抑制 Aurora B 来抑制。总之，这表明 Bub1 具有致癌特性，并暗示非整倍体和肿瘤发生是由 Aurora B 依赖性的错误分离引起的。在这里，我们专注于 Bub1 和 Aurora B 之间的复杂关系，并讨论了 Aurora B 的 Bub1 依赖性激活在介导错误校正中的更广泛意义。
