ABSTRACT

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.

摘要

转录因子 p53 响应多种压力刺激而被激活，以促进异常细胞的修复和存活或死亡。几十年来，执行肿瘤抑制基因 p53 的许多生物学功能的调控机制和下游目标主要集中在蛋白质编码基因的产物上。最近，发现了一类全新的分子，称为长链非编码 RNA (lncRNA)，它是塑造 p53 活性和生物学结果的关键调控因素。据报道，许多 p53 调控的 lncRNA 直接或间接干预 p53 调控网络，通常用于微调 p53 的肿瘤监测程序。最近的研究表明，聚集在 p53 上以调节其活性的信号和实现下游 p53 反应的分子包括蛋白质和 lncRNA。