BIOGRID CURATED DATA FOR PUBLICATION: MLF2 Negatively Regulates P53 and Promotes Colorectal Carcinogenesis.

Protein-Protein, Genetic, and Chemical Interactions for Fang D (2023):MLF2 Negatively Regulates P53 and Promotes Colorectal Carcinogenesis. curated by BioGRID (https://thebiogrid.org); ABSTRACT: 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.

蛋白质-蛋白质、遗传学以及化学相互作用数据集，针对方德（2023年）：MLF2通过负调控P53促进结直肠癌发生发展的研究，由BioGRID（https://thebiogrid.org）整理；摘要：p53途径的失活与多种人类癌症的发生密切相关。作为p53途径的关键组成部分，泛素特异性蛋白酶7（USP7）充当p53及其泛素E3连接酶小鼠双微体2同源物的去泛素化酶。本研究中，报告了髓系白血病因子2（MLF2）作为p53的新负调控因子。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。功能上，MLF2在结直肠癌中发挥致癌作用，至少部分是通过负调控p53实现的。临床研究表明，MLF2在结直肠癌中表达升高，其高表达与结直肠癌患者的预后不良相关。在含有野生型p53的结直肠癌中，MLF2和p53的表达呈负相关。这些发现将MLF2确立为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发展中的关键作用。