研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

解锁网关:核孔驱动的 p53 家族的时空动态及其对癌症治疗方法的影响。

Unlocking the Gateway: The Spatio-Temporal Dynamics of the p53 Family Driven by the Nuclear Pores and Its Implication for the Therapeutic Approach in Cancer.

发表日期:2024 Jul 07
作者: Dini Kurnia Ikliptikawati, Kei Makiyama, Masaharu Hazawa, Richard W Wong
来源: Epigenetics & Chromatin

摘要:

p53 家族仍然是当前大量研究的焦点。越来越多的证据表明 p53 异常是癌症中最常见的异常之一。鉴于现有的大量研究主要关注 p53 家族成员在不同恶性肿瘤中表现出的突变、表达谱和功能扰动,本综述将更多地关注有关核孔复合物 p53 激活和稳定的较少探索的方面。 NPC)在癌症中的作用,借鉴了多项研究。 p53 整合了广泛的信号,并受到多种调节机制的影响,以产生必要的细胞反应。人们普遍认为,p53 调节的每个阶段,从合成到降解,都会显着影响其执行特定任务的功能。近几十年来,大量数据已经证实,与蛋白质激活和稳定密切相关的调节机制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监管途径。这种新知识已经从基因本身的调控扩展到表观基因组学和蛋白质组学,与早期的范式相比,相互作用伙伴的数量和复杂性有所增加。具体来说,最近的研究表明 NPC 蛋白参与这种复杂的相互作用,进一步强调了 p53 调控的复杂性。此外,我们还讨论了基于该领域最新发展并结合已建立的靶向治疗的治疗策略。
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.