The MDM2-p53 pathway revisited.
The MDM2-p53 pathway revisited.
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DOI：
10.7555/jbr.27.20130030
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发表时间：
2013-07
影响因子：
2.3
通讯作者：
Zhang R
中科院分区：
文献类型：
--
作者：
Nag S;Qin J;Srivenugopal KS;Wang M;Zhang R
p53肿瘤抑制因子是调节DNA修复、细胞周期、细胞凋亡、血管生成和衰老等细胞途径的关键转录因子。它是对抗癌症发生和进展的重要防御机制，并通过与癌蛋白 MDM2 的相互作用进行负向调节。在人类癌症中，TP53基因经常发生突变或缺失，或者野生型p53功能被高水平的MDM2抑制，导致肿瘤抑制p53通路下调。因此，抑制MDM2-p53相互作用为治疗癌症提供了一种有吸引力的治疗策略。然而，最近的研究表明，MDM2-p53 相互作用更加复杂，涉及众多细胞蛋白和表观遗传机制的多个层面的调节，因此必须从整体角度重新审视这种复杂的相互作用。本综述旨在强调调节 MDM2-p53 轴的分子的多方面网络，以更好地了解该通路并将其用于抗癌治疗。
The p53 tumor suppressor is a key transcription factor regulating cellular pathways such as DNA repair, cell cycle, apoptosis, angiogenesis, and senescence. It acts as an important defense mechanism against cancer onset and progression, and is negatively regulated by interaction with the oncoprotein MDM2. In human cancers, the TP53 gene is frequently mutated or deleted, or the wild-type p53 function is inhibited by high levels of MDM2, leading to downregulation of tumor suppressive p53 pathways. Thus, the inhibition of MDM2-p53 interaction presents an appealing therapeutic strategy for the treatment of cancer. However, recent studies have revealed the MDM2-p53 interaction to be more complex involving multiple levels of regulation by numerous cellular proteins and epigenetic mechanisms, making it imperative to reexamine this intricate interplay from a holistic viewpoint. This review aims to highlight the multifaceted network of molecules regulating the MDM2-p53 axis to better understand the pathway and exploit it for anticancer therapy.