Xu Yuewei, Nijhuis Anke, Keun Hector C
Cancer Metabolism & Systems Toxicology Group, Division of Cancer, Department of Surgery and Cancer, Imperial College London, London, UK.
Br J Pharmacol. 2022 Jun;179(12):2795-2812. doi: 10.1111/bph.15331. Epub 2021 Jan 3.
RNA-binding motif protein 39 (RBM39) is an RNA-binding protein involved in transcriptional co-regulation and alternative RNA splicing. Recent studies have revealed that RBM39 is the unexpected target of aryl sulphonamides, which act as molecular glues between RBM39 and the DCAF15-associated E3 ubiquitin ligase complex leading to selective degradation of the target. Loss of RBM39 leads to aberrant splicing events and differential gene expression, thereby inhibiting cell cycle progression and causing tumour regression in a number of preclinical models. Many clinical studies have shown that aryl sulphonamides were well tolerated, but their clinical performance was limited due to an insufficient understanding of the target, RBM39 biology and a lack of predictive biomarkers. This review summarises the current knowledge of RBM39 function and discusses the therapeutic potential of this spliceosome target in cancer therapy. LINKED ARTICLES: This article is part of a themed issue on New avenues in cancer prevention and treatment (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.12/issuetoc.
RNA结合基序蛋白39（RBM39）是一种参与转录共调节和RNA可变剪接的RNA结合蛋白。最近的研究表明，RBM39是芳基磺酰胺的意外靶点，芳基磺酰胺充当RBM39与DCAF15相关的E3泛素连接酶复合物之间的分子胶，导致靶点的选择性降解。RBM39的缺失会导致异常剪接事件和基因表达差异，从而在一些临床前模型中抑制细胞周期进程并导致肿瘤消退。许多临床研究表明，芳基磺酰胺耐受性良好，但由于对靶点RBM39生物学了解不足以及缺乏预测性生物标志物，其临床疗效有限。本综述总结了目前关于RBM39功能的知识，并讨论了这个剪接体靶点在癌症治疗中的治疗潜力。相关文章：本文是关于癌症预防和治疗新途径（《英国药理学杂志》75周年）主题问题的一部分。要查看本节中的其他文章，请访问http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.12/issuetoc。
