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Selective Autophagy Regulates Cell Cycle in Cancer Therapy
Theranostics ( IF 12.4 ) Pub Date : 2019-01-01 , DOI: 10.7150/thno.30308
Kai Zheng , Zhendan He , Kaio Kitazato , Yifei Wang

Aberrant function of cell cycle regulators results in uncontrolled cell proliferation, making them attractive therapeutic targets in cancer treatment. Indeed, survival of many cancers exclusively relies on these proteins, and several specific inhibitors are in clinical use. Although the ubiquitin-proteasome system is responsible for the periodic quality control of cell cycle proteins during cell cycle progression, increasing evidence clearly demonstrates the intimate interaction between cell cycle regulation and selective autophagy, important homeostasis maintenance machinery. However, these studies have often led to divergent rather than unifying explanations due to complexity of the autophagy signaling network, the inconsistent functions between general autophagy and selective autophagy, and the different characteristics of autophagic substrates. In this review, we highlight current data illustrating the contradictory and important role of cell cycle proteins in regulating autophagy. We also focus on how selective autophagy acts as a central mechanism to maintain orderly DNA repair and genome integrity by degrading specific cell cycle proteins, regulating cell division, and promoting DNA damage repair. We further discuss the ways in which selective autophagy may impact the cell cycle regulators, since failure to appropriately remove these can interfere with cell death-related processes, including senescence and autophagy-related cell death. Imbalanced cell proliferation is typically utilized by cancer cells to acquire resistance. Finally, we discuss the possibility of a potent anticancer therapeutic strategy that targets selective autophagy or autophagy and cell cycle together.



中文翻译:

选择性自噬调节癌症治疗中的细胞周期

细胞周期调节剂的异常功能导致不受控制的细胞增殖,使其成为癌症治疗中有吸引力的治疗靶标。实际上,许多癌症的生存仅依赖于这些蛋白质,并且几种特定的抑制剂正在临床中使用。尽管泛素-蛋白酶体系统负责细胞周期进程中细胞周期蛋白的定期质量控制,但越来越多的证据清楚地表明了细胞周期调节与选择性自噬(重要的体内稳态维持机制)之间的密切相互作用。然而,由于自噬信号网络的复杂性,一般自噬与选择性自噬之间功能的不一致以及自噬底物的不同特性,这些研究常常导致分歧而不是统一的解释。在这篇综述中,我们重点介绍了目前的数据,这些数据说明了细胞周期蛋白在调节自噬中的矛盾和重要作用。我们还关注选择性自噬是如何通过降解特定的细胞周期蛋白,调节细胞分裂和促进DNA损伤修复来维持DNA修复和基因组完整性的有力机制。我们将进一步讨论选择性自噬可能影响细胞周期调节因子的方式,因为未能适当去除这些因子会干扰与细胞死亡相关的过程,包括衰老和与自噬相关的细胞死亡。癌细胞通常利用失衡的细胞增殖来获得抗性。最后,我们讨论了针对选择性自噬或自噬与细胞周期共同作用的有效抗癌治疗策略的可能性。

更新日期:2019-01-01
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