Pfleger C M, Salic A, Lee E, Kirschner M W
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Genes Dev. 2001 Jul 15;15(14):1759-64. doi: 10.1101/gad.897901.
Exit from mitosis requires the degradation of regulatory proteins including the mitotic cyclins and securin through ubiquitination by the anaphase promoting complex (APC) bound to Cdc20 or Cdh1. Cdc20-APC is regulated through inhibition by the spindle assembly checkpoint protein MAD2. Knowledge of Cdh1-APC regulation is limited to the phosphorylation-dependent dissociation of Cdh1 from APC. We report a novel means of regulating Cdh1 by the MAD2-related gene, MAD2L2. MAD2L2 specifically binds and inhibits Cdh1-APC, paralleling the effect of MAD2 on Cdc20. We suggest that MAD2L2 and MAD2 inhibit the release of substrates from APC and propose a mechanism of inhibition.
有丝分裂的退出需要通过与Cdc20或Cdh1结合的后期促进复合物(APC)进行泛素化作用,降解包括有丝分裂周期蛋白和分离酶抑制蛋白在内的调节蛋白。Cdc20-APC通过纺锤体组装检查点蛋白MAD2的抑制作用进行调节。关于Cdh1-APC调节的认识仅限于Cdh1从APC的磷酸化依赖性解离。我们报道了一种由MAD2相关基因MAD2L2调节Cdh1的新方法。MAD2L2特异性结合并抑制Cdh1-APC,这与MAD2对Cdc20的作用相似。我们认为MAD2L2和MAD2抑制底物从APC的释放,并提出了一种抑制机制。