Cells have evolved balanced mechanisms to protect themselves by initiating a specific response to a variety of stress. The TP53 gene, encoding P53 protein, is one of the many widely studied genes in human cells owing to its multifaceted functions and complex dynamics. The tumour-suppressing activity of P53 plays a principal role in the cellular response to stress. The majority of the human cancer cells exhibit the inactivation of the P53 pathway. In this review, we discuss the recent advancements in P53 research with particular focus on the role of P53 in DNA damage responses, apoptosis, autophagy, and cellular metabolism. We also discussed important P53-reactivation strategies that can play a crucial role in cancer therapy and the role of P53 in various diseases. We used electronic databases like PubMed and Google Scholar for literature search. In response to a variety of cellular stress such as genotoxic stress, ischemic stress, oncogenic expression, P53 acts as a sensor, and suppresses tumour development by promoting cell death or permanent inhibition of cell proliferation. It controls several genes that play a role in the arrest of the cell cycle, cellular senescence, DNA repair system, and apoptosis. P53 plays a crucial role in supporting DNA repair by arresting the cell cycle to purchase time for the repair system to restore genome stability. Apoptosis is essential for maintaining tissue homeostasis and tumour suppression. P53 can induce apoptosis in a genetically unstable cell by interacting with many pro-apoptotic and anti-apoptotic factors. Furthermore, P53 can activate autophagy, which also plays a role in tumour suppression. P53 also regulates many metabolic pathways of glucose, lipid, and amino acid metabolism. Thus under mild metabolic stress, P53 contributes to the cell’s ability to adapt to and survive the stress. These multiple levels of regulation enable P53 to perform diversified roles in many cell responses. Understanding the complete function of P53 is still a work in progress because of the inherent complexity involved in between P53 and its target proteins. Further research is required to unravel the mystery of this Guardian of the genome “TP53”.

中文翻译：

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探索基因组守护者的多重角色：P53

细胞已经进化出平衡机制来通过对各种压力发起特定反应来保护自己。TP53 基因编码 P53 蛋白，由于其多方面的功能和复杂的动力学，是人类细胞中众多被广泛研究的基因之一。P53 的肿瘤抑制活性在细胞对压力的反应中起主要作用。大多数人类癌细胞表现出 P53 途径的失活。在这篇综述中，我们讨论了 P53 研究的最新进展，特别关注 P53 在 DNA 损伤反应、细胞凋亡、自噬和细胞代谢中的作用。我们还讨论了可以在癌症治疗中发挥关键作用的重要 P53 再激活策略以及 P53 在各种疾病中的作用。我们使用 PubMed 和 Google Scholar 等电子数据库进行文献搜索。为应对各种细胞应激，如基因毒性应激、缺血应激、致癌表达，P53 充当传感器，通过促进细胞死亡或永久抑制细胞增殖来抑制肿瘤发展。它控制着几个在细胞周期停滞、细胞衰老、DNA 修复系统和细胞凋亡中起作用的基因。P53 通过阻止细胞周期为修复系统争取时间以恢复基因组稳定性，在支持 DNA 修复方面发挥着至关重要的作用。细胞凋亡对于维持组织稳态和肿瘤抑制至关重要。P53 可以通过与许多促凋亡和抗凋亡因子相互作用，在遗传不稳定的细胞中诱导凋亡。此外，P53 可以激活自噬，这也在肿瘤抑制中发挥作用。P53 还调节葡萄糖、脂质和氨基酸代谢的许多代谢途径。因此，在轻度代谢压力下，P53 有助于细胞适应压力并在压力下存活。这些多层次的调节使 P53 在许多细胞反应中发挥多样化的作用。由于 P53 与其靶蛋白之间存在固有的复杂性，因此了解 P53 的完整功能仍在进行中。需要进一步的研究来解开这个基因组守护者“TP53”的神秘面纱。由于 P53 与其靶蛋白之间存在固有的复杂性，因此了解 P53 的完整功能仍在进行中。需要进一步的研究来解开这个基因组守护者“TP53”的神秘面纱。由于 P53 与其靶蛋白之间存在固有的复杂性，因此了解 P53 的完整功能仍在进行中。需要进一步的研究来解开这个基因组守护者“TP53”的神秘面纱。