Damizia Michela, Moretta Gian Mario, De Wulf Peter
Department of Cellular, Computational, and Integrative Biology (CIBIO), University of Trento, 38123, Trento (TN), Italy.
Cell Death Discov. 2023 Nov 7;9(1):410. doi: 10.1038/s41420-023-01704-7.
By responding to a host of adverse conditions, ranging from DNA damage to viral infection, transcription factor p53 supports genomic stability, cellular health, and survival. Not surprisingly, tumours across the cancer spectrum carry mutations in p53, misexpress the protein, or dysregulate its activity. Several signalling pathways, many of which comprise oncogenic proteins, converge upon p53 to control its stability and activity. We here present the conserved kinase/ATPase RioK1 as an upstream factor that determines p53 activity at the DNA, RNA, and protein levels. It achieves this task by integrating the regulatory events that act on p53 into a coherent response circuit. We will also discuss how RIOK1 overexpression represents an alternative mechanism for cancers to inactivate p53, and how targeting RioK1 could eradicate malignancies that are driven by a dysregulated RioK1-p53 network.
通过应对从DNA损伤到病毒感染等一系列不利条件，转录因子p53维持基因组稳定性、细胞健康和生存。毫不奇怪，各种癌症中的肿瘤都携带p53突变、错误表达该蛋白或使其活性失调。若干信号通路（其中许多包含致癌蛋白）汇聚于p53以控制其稳定性和活性。我们在此提出保守的激酶/ATP酶RioK1作为一个上游因子，它在DNA、RNA和蛋白质水平上决定p53的活性。它通过将作用于p53的调控事件整合到一个连贯的反应回路中来完成这项任务。我们还将讨论RIOK1的过表达如何代表癌症使p53失活的另一种机制，以及靶向RioK1如何根除由失调的RioK1-p53网络驱动的恶性肿瘤。
