Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Cell Death Dis. 2018 Feb 7;9(2):186. doi: 10.1038/s41419-017-0208-z.
As one of the most important post-translational modifications, ubiquitination plays versatile roles in cancer-related pathways, and is involved in protein metabolism, cell-cycle progression, apoptosis, and transcription. Counteracting the activities of the E3 ligases, the deubiquitylating enzymes have been suggested as another important mechanism to modulate the ubiquitination process, and are implicated in cancer as well. In this article, we review the emerging roles of USP28 in cancer pathways as revealed by recent studies. We discuss the major mechanisms by which USP28 is involved in the cancer-related pathways, whereby USP28 regulates physiological homeostasis of ubiquitination process, DNA-damage response, and cell cycle during genotoxic stress. We further review the studies where USP28 was targeted for treating multiples cancers including non-small cell lung cancer, breast cancer, intestinal cancers, gliomas, and bladder cancer. As a result, the clinical significance of targeting USP28 for cancer therapy merits further exploration and demonstration.
作为最重要的翻译后修饰之一，泛素化在癌症相关途径中发挥着多种作用，涉及蛋白质代谢、细胞周期进程、细胞凋亡和转录。去泛素化酶通过拮抗 E3 连接酶的作用，被认为是另一种调节泛素化过程的重要机制，也与癌症有关。在本文中，我们综述了最近的研究揭示的 USP28 在癌症途径中的新作用。我们讨论了 USP28 参与癌症相关途径的主要机制，包括 USP28 如何调节泛素化过程、DNA 损伤反应以及细胞周期在遗传毒性应激下的生理平衡。我们还回顾了 USP28 被用于治疗多种癌症的研究，包括非小细胞肺癌、乳腺癌、肠道癌症、神经胶质瘤和膀胱癌。因此，针对 USP28 进行癌症治疗的临床意义值得进一步探索和论证。
