In mitosis and meiosis, chromosome segregation is triggered by the Anaphase-Promoting Complex/Cyclosome (APC/C), a multi-subunit ubiquitin ligase that targets proteins for degradation, leading to the separation of chromatids. APC/C activation requires phosphorylation of its APC3 and APC1 subunits, which allows the APC/C to bind its co-activator Cdc20. The identity of the kinase(s) responsible for APC/C activation in vivo is unclear. Cyclin B3 (CycB3) is an activator of the Cyclin-Dependent Kinase 1 (Cdk1) that is required for meiotic anaphase in flies, worms and vertebrates. It has been hypothesized that CycB3-Cdk1 may be responsible for APC/C activation in meiosis but this remains to be determined. Using Drosophila, we found that mutations in CycB3 genetically enhance mutations in tws, which encodes the B55 regulatory subunit of Protein Phosphatase 2A (PP2A) known to promote mitotic exit. Females heterozygous for CycB3 and tws loss-of-function alleles lay embryos that arrest in mitotic metaphase in a maternal effect, indicating that CycB3 promotes anaphase in mitosis in addition to meiosis. This metaphase arrest is not due to the Spindle Assembly Checkpoint (SAC) because mutation of mad2 that inactivates the SAC does not rescue the development of embryos from CycB3^-/+, tws^-/+ females. Moreover, we found that CycB3 promotes APC/C activity and anaphase in cells in culture. We show that CycB3 physically associates with the APC/C, is required for phosphorylation of APC3, and promotes APC/C association with its Cdc20 co-activators Fizzy and Cortex. Our results strongly suggest that CycB3-Cdk1 directly activates the APC/C to promote anaphase in both meiosis and mitosis.

在有丝分裂和减数分裂中，染色体分离是由促进后期的复合物/ Cyclosome（APC / C）引发的，APC / C是一种多亚单位的泛素连接酶，其靶向蛋白质进行降解，从而导致染色单体的分离。APC / C激活需要对其APC3和APC1亚基进行磷酸化，这使APC / C可以结合其辅助激活剂Cdc20。目前尚不清楚负责APC / C体内激活的激酶的身份。细胞周期蛋白B3（CycB3）是细胞周期蛋白依赖性激酶1（Cdk1）的激活剂，它是果蝇，蠕虫和脊椎动物减数分裂后期所必需的。假设CycB3-Cdk1可能是减数分裂中APC / C活化的原因，但这仍有待确定。使用果蝇，我们发现CycB3中的突变遗传上增强了tws的突变，该突变编码已知可促进有丝分裂退出的蛋白磷酸酶2A（PP2A）的B55调节亚基。CycB3和tws功能丧失等位基因杂合的雌性产卵的胚胎在母体效应中停在有丝分裂中期，这表明CycB3除减数分裂外还促进有丝分裂后期。此中期停滞不是由于纺锤体装配检查点（SAC）所致，因为使SAC失活的mad2突变不能挽救CycB3- ^{/ +}，tws- ^{/ +}的胚胎发育女性。此外，我们发现CycB3在培养的细胞中促进APC / C活性和后期。我们显示CycB3物理上与APC / C缔合，是APC3磷酸化所必需的，并促进APC / C与Cdc20共激活剂Fizzy和Cortex缔合。我们的结果强烈表明CycB3-Cdk1直接激活APC / C促进减数分裂和有丝分裂后期的后期。