Chen Xuankun, Jiang Li, Zhou Zhesheng, Yang Bo, He Qiaojun, Zhu Chengliang, Cao Ji
Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Institute of Pharmacology and Toxicology, Zhejiang University, Hangzhou, China.
The Innovation Institute for Artificial Intelligence in Medicine, Zhejiang University, Hangzhou, China.
Front Pharmacol. 2022 Jul 1;13:928794. doi: 10.3389/fphar.2022.928794. eCollection 2022.
The cell membrane system comprises the plasma membrane, endoplasmic reticulum, Golgi apparatus, lysosome, mitochondria, and nuclear membrane, which are essential for maintaining normal physiological functions of cells. The proteins associated with these membrane-organelles are frequently modified to regulate their functions, the most common of which is ubiquitin modification. So far, many ubiquitin E3 ligases anchored in the membrane system have been identified as critical players facilitating intracellular biofunctions whose dysfunction is highly related to cancer. In this review, we summarized membrane-associated E3 ligases and revealed their relationship with cancer, which is of great significance for discovering novel drug targets of cancer and may open up new avenues for inducing ubiquitination-mediated degradation of cancer-associated membrane proteins small chemicals such as PROTAC and molecular glue.
细胞膜系统由质膜、内质网、高尔基体、溶酶体、线粒体和核膜组成，这些对于维持细胞的正常生理功能至关重要。与这些膜细胞器相关的蛋白质经常被修饰以调节其功能，其中最常见的是泛素修饰。到目前为止，许多锚定在膜系统中的泛素E3连接酶已被确定为促进细胞内生物功能的关键参与者，其功能障碍与癌症高度相关。在本综述中，我们总结了膜相关E3连接酶，并揭示了它们与癌症的关系，这对于发现癌症的新型药物靶点具有重要意义，并且可能为诱导泛素化介导的癌症相关膜蛋白降解开辟新途径，如PROTAC和分子胶等小分子化合物。
