Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson UT Health Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
RNA Biol. 2020 Nov;17(11):1648-1656. doi: 10.1080/15476286.2020.1770981. Epub 2020 Jun 4.
Transcription factor p53 is activated in response to numerous stress stimuli in order to promote repair and survival or death of abnormal cells. For decades, regulatory mechanisms and downstream targets that execute the many biological functions of tumour suppressor p53 largely focused on the products of protein-coding genes. Recently, an entirely new class of molecules, termed long non-coding RNAs (lncRNAs), were discovered as key regulatory players in shaping p53 activity and biological outcomes. Many p53-regulated lncRNAs are now reported to either directly or indirectly intervene in p53-regulatory networks, generally in fine-tuning p53's tumour surveillance programme. Recent studies reveal that signals that converge upon p53 to regulate its activity, and molecules that implement downstream p53-response include both proteins and lncRNAs. In this review, we discuss the non-proteomic component of p53-regulatory networks, focusing on lncRNAs regulated by p53 and/or that regulate p53 activity, and their impact on biological outcomes.
转录因子 p53 会被多种应激刺激激活,以促进异常细胞的修复和存活或死亡。几十年来,执行肿瘤抑制因子 p53 多种生物学功能的调控机制和下游靶标主要集中在蛋白质编码基因的产物上。最近,一类全新的分子,即长非编码 RNA(lncRNA),被发现是调节 p53 活性和生物学结果的关键调控因子。现在有许多报道称,p53 调控的 lncRNA 要么直接、要么间接地干预 p53 调控网络,通常是在微调 p53 的肿瘤监测计划。最近的研究表明,作用于 p53 以调节其活性的信号,以及执行下游 p53 反应的分子,既包括蛋白质,也包括 lncRNA。在这篇综述中,我们讨论了 p53 调控网络的非蛋白质组成分,重点讨论了受 p53 调控和/或调节 p53 活性的 lncRNA,以及它们对生物学结果的影响。