College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea.
Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Cells. 2020 Sep 16;9(9):2107. doi: 10.3390/cells9092107.
The tumor suppressor p53 acts as a transcription factor that regulates the expression of a number of genes responsible for DNA repair, cell cycle arrest, metabolism, cell migration, angiogenesis, ferroptosis, senescence, and apoptosis. It is the most commonly silenced or mutated gene in cancer, as approximately 50% of all types of human cancers harbor TP53 mutations. Activation of p53 is detrimental to normal cells, thus it is tightly regulated via multiple mechanisms. One of the recently identified regulators of p53 is RNA-binding motif protein 10 (RBM10). RBM10 is an RNA-binding protein frequently deleted or mutated in cancer cells. Its loss of function results in various deformities, such as cleft palate and malformation of the heart, and diseases such as lung adenocarcinoma. In addition, RBM10 mutations are frequently observed in lung adenocarcinomas, colorectal carcinomas, and pancreatic ductal adenocarcinomas. RBM10 plays a regulatory role in alternative splicing. Several recent studies not only linked this splicing regulation of RBM10 to cancer development, but also bridged RBM10's anticancer function to the p53 pathway. This review will focus on the current progress in our understanding of RBM10 regulation of p53, and its role in p53-dependent cancer prevention.
抑癌基因 p53 作为转录因子，调节负责 DNA 修复、细胞周期停滞、代谢、细胞迁移、血管生成、铁死亡、衰老和细胞凋亡的多种基因的表达。它是癌症中最常被沉默或突变的基因，因为大约 50%的人类癌症都存在 TP53 突变。p53 的激活对正常细胞是有害的，因此它通过多种机制受到严格调控。最近发现的 p53 调节因子之一是 RNA 结合基序蛋白 10（RBM10）。RBM10 是一种在癌细胞中经常缺失或突变的 RNA 结合蛋白。其功能丧失会导致各种畸形，如腭裂和心脏畸形，以及肺癌等疾病。此外，RBM10 突变在肺腺癌、结直肠癌和胰腺导管腺癌中经常观察到。RBM10 在可变剪接中起调节作用。最近的几项研究不仅将 RBM10 的这种剪接调控与癌症的发生联系起来，还将 RBM10 的抗癌功能与 p53 途径联系起来。这篇综述将重点介绍我们对 RBM10 对 p53 调节的理解的最新进展，以及它在 p53 依赖性癌症预防中的作用。
