Greil Christine, Engelhardt Monika, Wäsch Ralph
Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, Medical Center-University of Freiburg, Freiburg, Germany.
Front Genet. 2022 Jun 27;13:941565. doi: 10.3389/fgene.2022.941565. eCollection 2022.
To sustain genomic stability by correct DNA replication and mitosis, cell cycle progression is tightly controlled by the cyclic activity of cyclin-dependent kinases, their binding to cyclins in the respective phase and the regulation of cyclin levels by ubiquitin-dependent proteolysis. The spindle assembly checkpoint plays an important role at the metaphase-anaphase transition to ensure a correct separation of sister chromatids before cytokinesis and to initiate mitotic exit, as an incorrect chromosome distribution may lead to genetically unstable cells and tumorigenesis. The ubiquitin ligase anaphase-promoting complex or cyclosome (APC/C) is essential for these processes by mediating the proteasomal destruction of cyclins and other important cell cycle regulators. To this end, it interacts with the two regulatory subunits Cdh1 and Cdc20. Both play a role in tumorigenesis with Cdh1 being a tumor suppressor and Cdc20 an oncogene. In this review, we summarize the current knowledge about the APC/C-regulators Cdh1 and Cdc20 in tumorigenesis and potential targeted therapeutic approaches.
为了通过正确的DNA复制和有丝分裂维持基因组稳定性，细胞周期进程受到细胞周期蛋白依赖性激酶的周期性活性、它们在各自阶段与细胞周期蛋白的结合以及通过泛素依赖性蛋白水解对细胞周期蛋白水平的调控的严格控制。纺锤体组装检查点在中期-后期转换过程中发挥重要作用，以确保在胞质分裂前姐妹染色单体正确分离并启动有丝分裂退出，因为不正确的染色体分布可能导致基因不稳定的细胞和肿瘤发生。泛素连接酶后期促进复合物或细胞周期体（APC/C）通过介导细胞周期蛋白和其他重要细胞周期调节因子的蛋白酶体降解，对这些过程至关重要。为此，它与两个调节亚基Cdh1和Cdc20相互作用。两者在肿瘤发生中都起作用，Cdh1是一种肿瘤抑制因子，Cdc20是一种癌基因。在这篇综述中，我们总结了目前关于APC/C调节因子Cdh1和Cdc20在肿瘤发生中的知识以及潜在的靶向治疗方法。
