Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1

Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1
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DOI:
10.1016/s1097-2765(00)80126-4
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发表时间:
1998-08-01
期刊:
影响因子:
16
通讯作者:
Kirschner, MW
Kirschner, MW
中科院分区:
生物学1区
文献类型:
--
作者:
Fang, GW;Yu, HT;Kirschner, MW

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后期促进复合体(APC)的激活是后期起始和有丝分裂退出所必需的。我们发现APC在有丝分裂和G1期间被两个调节因子hCDC20和hCDH1激活。这些蛋白直接与APC结合并激活其细胞周期蛋白泛素化活性。hCDC20对APC具有严格的破坏盒(D-box)依赖性,而hCDH1对D-box具有更宽松的特异性。在HeLa细胞中,hCDC20蛋白水平及其与APC的结合在有丝分裂时达到峰值,并在G1早期急剧下降。因此,hCDC20是APC的有丝分裂激活剂,并指导含有D-box的底物的降解。hCDH1蛋白水平在细胞周期中保持不变,并可能靶向G1中缺乏D-box的特定底物,如polo样激酶,进行泛素化。
Activation of the anaphase-promoting complex (APC) is required for anaphase initiation and for exit from mitosis. We show that APC is activated during mitosis and G1 by two regulatory factors, hCDC20 and hCDH1. These proteins directly bind to APC and activate its cyclin ubiquitination activity. hCDC20 confers a strict destruction-box (D-box) dependence on APC, while hCDH1 shows a much more relaxed specificity for the D-box. In HeLa cells, the protein levels of hCDC20 as well as its binding to APC peak in mitosis and decrease drastically at early G1. Thus, hCDC20 is the mitotic activator of APC and directs the degradation of substrates containing the D-box. The hCDH1 protein level remains constant during the cell cycle and may target specific substrates lacking the D-box in G1, such as polo-like kinase, for ubiquitination.