Li Xian-Miao, Zhao Zhen-Yu, Yu Xiao, Xia Qi-Dong, Zhou Peng, Wang Shao-Gang, Wu Huan-Lei, Hu Jia
Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Liberalization Ave, No. 1095, Wuhan, 430030, China.
Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Exp Hematol Oncol. 2023 Mar 30;12(1):34. doi: 10.1186/s40164-023-00394-2.
Tumor development relies on a complex and aberrant tissue environment in which cancer cells receive the necessary nutrients for growth, survive through immune escape, and acquire mesenchymal properties that mediate invasion and metastasis. Stromal cells and soluble mediators in the tumor microenvironment (TME) exhibit characteristic anti-inflammatory and protumorigenic activities. Ubiquitination, which is an essential and reversible posttranscriptional modification, plays a vital role in modulating the stability, activity and localization of modified proteins through an enzymatic cascade. This review was motivated by accumulating evidence that a series of E3 ligases and deubiquitinases (DUBs) finely target multiple signaling pathways, transcription factors and key enzymes to govern the functions of almost all components of the TME. In this review, we systematically summarize the key substrate proteins involved in the formation of the TME and the E3 ligases and DUBs that recognize these proteins. In addition, several promising techniques for targeted protein degradation by hijacking the intracellular E3 ubiquitin-ligase machinery are introduced.
肿瘤的发展依赖于复杂且异常的组织环境，在此环境中癌细胞获取生长所需的营养物质，通过免疫逃逸存活，并获得介导侵袭和转移的间充质特性。肿瘤微环境（TME）中的基质细胞和可溶性介质表现出典型的抗炎和促肿瘤活性。泛素化是一种重要的可逆转录后修饰，通过酶促级联反应在调节修饰蛋白的稳定性、活性和定位方面发挥着至关重要的作用。一系列E3连接酶和去泛素化酶（DUB）精细地靶向多种信号通路、转录因子和关键酶，以调控TME几乎所有组分的功能，这一不断积累的证据促使了本综述的撰写。在本综述中，我们系统地总结了参与TME形成的关键底物蛋白以及识别这些蛋白的E3连接酶和DUB。此外，还介绍了几种通过劫持细胞内E3泛素连接酶机制进行靶向蛋白降解的有前景的技术。
