Elliott Joanne, Hookham Michelle B, Johnston James A
Infection and Immunity Group, Centre for Cancer Research and Cell Biology, School of Biomedical Sciences, Faculty of Medicine, Health and Life Sciences, Queen's University, Whitla Medical Building, Belfast BT9 7BL, N. Ireland, UK.
Biochem Soc Trans. 2008 Jun;36(Pt 3):464-8. doi: 10.1042/BST0360464.
Many studies have suggested that E3 ubiquitin ligases can behave as either oncogenes or tumour suppressor genes and, recently, it has become clear that the SOCS (suppressor of cytokine signalling) E3 ligases fit this mould. While most cancer-associated E3s regulate the cell cycle or DNA repair, the SOCS proteins inhibit growth factor responses by degrading signalling intermediates such as JAKs (Janus kinases) via the SOCS-box-associated ECS (Elongin-Cullin-SOCS) E3 ligase. Clinical studies have found that (epi)genetic (mutation or methylation) phenomena can occur in many solid tumours and a growing number of clinical findings reveal post-translational modifications that disrupt SOCS function in haematological malignancy. In the present review, we provide a summary of the functions of the SOCS E3s and propose the potential use of members of this family as diagnostic markers and therapeutic targets in cancer.
许多研究表明，E3泛素连接酶既可以充当癌基因，也可以作为肿瘤抑制基因，最近，很明显细胞因子信号转导抑制因子（SOCS）E3连接酶也符合这种模式。虽然大多数与癌症相关的E3调节细胞周期或DNA修复，但SOCS蛋白通过与SOCS盒相关的ECS（延伸蛋白-库林-SOCS）E3连接酶降解信号中间体（如JAKs，即Janus激酶）来抑制生长因子反应。临床研究发现，（表观）遗传（突变或甲基化）现象可发生于许多实体瘤中，越来越多的临床研究结果揭示了在血液系统恶性肿瘤中破坏SOCS功能的翻译后修饰。在本综述中，我们总结了SOCS E3的功能，并提出该家族成员作为癌症诊断标志物和治疗靶点的潜在用途。
