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Updated: Jul 26, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

p53和YY1之间的竞争决定了膀癌中PHGDH表达和恶性瘤的发生

Tiezhu Shi^1,2, Zhihao Yuan², Yanying He¹

¹Precise Genome Engineering Centre, School of Life Sciences, Guangzhou University, 510006, Guangzhou, China.

Cellular oncology (Dordrecht, Netherlands)

|June 16, 2023

概括

膀癌中的突变p53通过通过YY1.1.驱动血清蛋白合成途径表达促进瘤生长. 野生类型的p53通常会抑制这种途径,但在突变时会失去控制.

科学领域:

在瘤学瘤学.
代谢途径代谢途径
癌症生物学癌症生物学

背景情况:

在癌症中,血清酶代谢往往是失调的.
瘤抑制剂p53与调节血清代谢有关,但机制尚不清楚.
研究p53在血清合成中的作用对于了解膀癌至关重要.

研究的目的:

阐明p53在调节膀癌 (BLCA) 中的血清素合成途径 (SSP) 中的作用和机制.
了解p53状态 (野生型与突变型) 如何影响SSP和瘤生长.

主要方法:

用CRISPR/Cas9和LC-MS/MS.比较BLCA细胞系与野生型 (WT) 和突变p53的代谢概况.
分析了癌症基因组图谱 (TCGA) 和基因表达总汇 (GEO) 数据集的PHGDH表达.
使用异种移植模型,染色体免疫沉 (ChIP) 和YY1/p53/SIRT1相互作用试验.

主要成果:

在p53-突变BLCA细胞中,SSP显著改变.
在BLCA中,TP53突变与增加的PHGDH表达相关.
在小鼠中,PHGDH 枯竭会影响瘤生长和活性氧物种恒温.
通过SIRT1招募,WT p53抑制PHGDH;YY1和p53竞争PHGDH促进体结合.

结论:

在突变的p53BLCA中,YY1驱动PHGDH表达,促进瘤发生.
这项竞争性法规解释了p53突变与膀癌中改变的血清代谢之间的联系.

关键词:

膀癌是一种癌症.PHGDH PHGDH 的时间血清蛋白的代谢过程 YY1 YY1 这是一个很大的问题.这就是p53突变.

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