Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China.
Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, Bengbu Medical College, Anhui, 233030, China; The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Cancer Lett. 2023 Apr 28;560:216128. doi: 10.1016/j.canlet.2023.216128. Epub 2023 Mar 16.
Posttranslational modifications (PTMs), such as phosphorylation, methylation, ubiquitination, and acetylation, are important in governing protein expression levels. Proteolysis targeting chimeras (PROTACs) are novel structures designed to target a protein of interest (POI) for ubiquitination and degradation, leading to the selective reduction in the expression levels of the POI. PROTACs have exhibited great promise due to their ability to target undruggable proteins, including several transcription factors. Recently, PROTACs have been characterized to improve anticancer immunotherapy via the regulation of specific proteins. In this review, we describe how the PROTACs target several molecules, including HDAC6, IDO1, EGFR, FoxM1, PD-L1, SHP2, HPK1, BCL-xL, BET proteins, NAMPT, and COX-1/2, to regulate immunotherapy in human cancers. PROTACs may provide potential treatment benefits by enhancing immunotherapy in cancer patients.
翻译后修饰（PTM），如磷酸化、甲基化、泛素化和乙酰化，在调控蛋白质表达水平方面起着重要作用。靶向嵌合体（PROTAC）是一种新型结构，旨在将目标蛋白（POI）靶向泛素化和降解，从而导致POI表达水平的选择性降低。PROTAC因其能够靶向难以成药的蛋白质（包括几种转录因子）而展现出巨大的潜力。最近，PROTAC已被证明可通过调节特定蛋白质来改善抗癌免疫疗法。在本综述中，我们描述了PROTAC如何靶向包括HDAC6、IDO1、EGFR、FoxM1、PD-L1、SHP2、HPK1、BCL-xL、BET蛋白、NAMPT和COX-1/2在内的多种分子，以调节人类癌症中的免疫疗法。PROTAC可能通过增强癌症患者的免疫疗法提供潜在的治疗益处。
