MLF2 Negatively Regulates P53 and Promotes Colorectal Carcinogenesis,Advanced Science

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MLF2 Negatively Regulates P53 and Promotes Colorectal Carcinogenesis
Advanced Science ( IF 14.3 ) Pub Date : 2023-07-12 , DOI: 10.1002/advs.202303336
Debao Fang _{1,

2} , Hao Hu ₂ , Kailiang Zhao _{1,

2} , Aman Xu ₃ , Changjun Yu ₃ , Yong Zhu ₃ , Ning Yu ₂ , Bo Yao ₂ , Suyun Tang ₂ , Xianning Wu ₁ , Yide Mei _{1,

2,

4}

Affiliation

Inactivation of the p53 pathway is linked to a variety of human cancers. As a critical component of the p53 pathway, ubiquitin-specific protease 7 (USP7) acts as a deubiquitinase for both p53 and its ubiquitin E3 ligase mouse double minute 2 homolog. Here, myeloid leukemia factor 2 (MLF2) is reported as a new negative regulator of p53. MLF2 interacts with both p53 and USP7. Via these interactions, MLF2 inhibits the binding of USP7 to p53 and antagonizes USP7-mediated deubiquitination of p53, thereby leading to p53 destabilization. Functionally, MLF2 plays an oncogenic role in colorectal cancer, at least partially, via the negative regulation of p53. Clinically, MLF2 is elevated in colorectal cancer and its high expression is associated with poor prognosis in patients with colorectal cancer. In wild-type-p53-containing colorectal cancer, MLF2 and p53 expressions are inversely correlated. These findings establish MLF2 as an important suppressor of p53 function. The study also reveals a critical role for the MLF2–p53 axis in promoting colorectal carcinogenesis.

中文翻译：

MLF2 负调控 P53 促进结直肠癌发生

p53 通路失活与多种人类癌症有关。作为 p53 通路的关键组成部分，泛素特异性蛋白酶 7 (USP7) 充当 p53 及其泛素 E3 连接酶小鼠双分钟 2 同源物的去泛素酶。据报道，髓系白血病因子 2 (MLF2) 是 p53 的新负调节因子。MLF2 与 p53 和 USP7 相互作用。通过这些相互作用，MLF2 抑制 USP7 与 p53 的结合，并拮抗 USP7 介导的 p53 去泛素化，从而导致 p53 不稳定。从功能上来说，MLF2 在结直肠癌中发挥致癌作用，至少部分是通过 p53 的负调控实现的。临床上，MLF2在结直肠癌中升高，其高表达与结直肠癌患者的不良预后相关。在含有野生型 p53 的结直肠癌中，MLF2 和 p53 表达呈负相关。这些发现表明 MLF2 是 p53 功能的重要抑制因子。该研究还揭示了 MLF2-p53 轴在促进结直肠癌发生中的关键作用。

更新日期：2023-07-12

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