PDF(Pubmed)
Abstract：
The p53 family remains a captivating focus of an extensive number of current studies. Accumulating evidence indicates that p53 abnormalities rank among the most prevalent in cancer. Given the numerous existing studies, which mostly focus on the mutations, expression profiles, and functional perturbations exhibited by members of the p53 family across diverse malignancies, this review will concentrate more on less explored facets regarding p53 activation and stabilization by the nuclear pore complex (NPC) in cancer, drawing on several studies. p53 integrates a broad spectrum of signals and is subject to diverse regulatory mechanisms to enact the necessary cellular response. It is widely acknowledged that each stage of p53 regulation, from synthesis to degradation, significantly influences its functionality in executing specific tasks. Over recent decades, a large body of data has established that mechanisms of regulation, closely linked with protein activation and stabilization, involve intricate interactions with various cellular components. These often transcend canonical regulatory pathways. This new knowledge has expanded from the regulation of genes themselves to epigenomics and proteomics, whereby interaction partners increase in number and complexity compared with earlier paradigms. Specifically, studies have recently shown the involvement of the NPC protein in such complex interactions, underscoring the further complexity of p53 regulation. Furthermore, we also discuss therapeutic strategies based on recent developments in this field in combination with established targeted therapies.
摘要：
p53家族仍然是当前大量研究的迷人焦点。越来越多的证据表明p53异常是癌症中最普遍的。鉴于现有的大量研究，主要集中在突变上，表达式配置文件,以及p53家族成员在不同恶性肿瘤中表现出的功能扰动，这篇综述将更多地集中在关于癌症中核孔复合物（NPC）的p53激活和稳定的较少探索的方面，借鉴了几项研究。p53整合了广谱的信号，并受到多种调节机制的影响，以产生必要的细胞反应。众所周知，p53调控的每个阶段，从合成到降解，显着影响其执行特定任务的功能。近几十年来,大量数据已经建立了监管机制，与蛋白质活化和稳定密切相关，涉及与各种细胞成分的复杂相互作用。这些通常超越规范的调节途径。这种新知识已经从基因本身的调控扩展到了表观基因组学和蛋白质组学,与早期的范例相比，交互伙伴的数量和复杂性增加。具体来说,最近的研究表明，NPC蛋白参与了这种复杂的相互作用，强调了p53调控的进一步复杂性。此外，我们还讨论了基于该领域最新发展的治疗策略,并结合已建立的靶向治疗.
