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肾细胞癌中的p53及其异构体——它们重要吗?

p53 and Its Isoforms in Renal Cell Carcinoma-Do They Matter?

作者信息

Swiatkowska Agata

机构信息

Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, Poland.

出版信息

Biomedicines. 2022 Jun 6;10(6):1330. doi: 10.3390/biomedicines10061330.

Abstract

p53 is a transcription al factor responsible for the maintenance of cellular homeostasis. It has been shown that more than 50% of tumors are connected with mutations in the gene. These mutations cause a disturbance in cellular response to stress, and eventually, cancer development. Apart from the full-length p53, at least twelve isoforms of p53 have been characterized. They are able to modulate p53 activity under stress conditions. In 2020, almost a half of million people around the world were diagnosed with renal cancer. One genetic disturbance which is linked to the most common type of kidney cancer, renal cell carcinoma, RCC, occurs from mutations in the gene. Recent data has revealed that the VHL protein is needed to fully activate p53. Disturbance of the interplay between p53 and VHL seems to explain the lack of efficient response to chemotherapy in RCC. Moreover, it has been observed that changes in the expression of p53 isoforms are associated with different stages of RCC and overall survival. Thus, herein, an attempt was made to answer the question whether p53 and its isoforms are important factors in the development of RCC on the one hand, and in positive response to anti-RCC therapy on the other hand.

摘要

p53是一种负责维持细胞稳态的转录因子。已有研究表明,超过50%的肿瘤与该基因的突变有关。这些突变会导致细胞对应激的反应紊乱,并最终引发癌症。除了全长p53外,至少已鉴定出12种p53异构体。它们能够在应激条件下调节p53的活性。2020年,全球近50万人被诊断出患有肾癌。一种与最常见的肾癌类型——肾细胞癌(RCC)相关的基因紊乱是由该基因的突变引起的。最近的数据显示,VHL蛋白是完全激活p53所必需的。p53与VHL之间相互作用的紊乱似乎可以解释RCC对化疗缺乏有效反应的原因。此外,据观察,p53异构体表达的变化与RCC的不同阶段及总生存期相关。因此,本文试图回答这样一个问题,即p53及其异构体一方面是否是RCC发生发展的重要因素,另一方面是否是RCC抗治疗产生阳性反应的重要因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9959/9219959/3549fcd7b955/biomedicines-10-01330-g001.jpg

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