Weaver Beth A A, Cleveland Don W
Department of Pharmacology, University of Wisconsin-Madison, Madison, WI 53562, USA.
J Cell Biol. 2009 Jun 15;185(6):935-7. doi: 10.1083/jcb.200905098.
Impaired mitotic checkpoint signaling can both promote and suppress tumors. The mitotic checkpoint targets Cdc20, the specificity factor of the ubiquitin ligase that promotes anaphase by targeting cyclin B and securin for destruction. In this issue, Li et al. (2009. J. Cell Biol. doi:10.1083/jcb.200904020) use gene replacement to produce mice expressing a Cdc20 mutant that cannot be inhibited by the mitotic checkpoint. In addition to the expected aneuploidy, these animals have a high tumor incidence that is likely caused by persistent aneuploidy coupled with nonmitotic functions of mutant Cdc20.
有丝分裂检查点信号受损既能促进肿瘤发生,也能抑制肿瘤。有丝分裂检查点作用于Cdc20,它是泛素连接酶的特异性因子,通过靶向细胞周期蛋白B和securin进行降解来促进后期。在本期中,Li等人(2009年。《细胞生物学杂志》。doi:10.1083/jcb.200904020)利用基因替换技术培育出表达一种不能被有丝分裂检查点抑制的Cdc20突变体的小鼠。除了预期的非整倍体外,这些动物的肿瘤发生率很高,这可能是由持续的非整倍体以及突变型Cdc20的非有丝分裂功能导致的。