PHLDA1 is a P53 target gene involved in P53-mediated cell apoptosis.

Autor: Song X; Center for Cancer Research, Shantou University Medical College, Shantou, Guangdong, China.; Section of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, China., Zhou L; Section of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, China., Yang W; Section of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, China., Li X; Section of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, China., Ma J; Section of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, China., Qi K; Section of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, China., Liang R; Section of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, China., Li M; Section of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, China., Xie L; Section of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, China., Su T; Section of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, China., Huang D; Section of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, China. huangdy@stu.edu.cn., Liang B; Section of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, China. bliang@stu.edu.cn.; Biomedical Research Center, Shantou University Medical College, Shantou, Guangdong, China. bliang@stu.edu.cn.
Jazyk: angličtina
Zdroj: Molecular and cellular biochemistry [Mol Cell Biochem] 2024 Mar; Vol. 479 (3), pp. 653-664. Date of Electronic Publication: 2023 May 08.
DOI: 10.1007/s11010-023-04752-w
Abstrakt: Pleckstrin homeolike domain, family A, member 1 (PHLDA1) is a multifunctional protein that plays diverse roles in A variety of biological processes, including cell death, and hence its altered expression has been found in different types of cancer. Although studies have shown a regulatory relationship between p53 and PHLDA1, the molecular mechanism is still unclear. Especially, the role of PHLDA1 in the process of apoptosis is still controversial. In this study, we found that the expression of PHLDA1 in human cervical cancer cell lines was correlated with the up-expression of p53 after treatment with apoptosis-inducing factors. Subsequently, the binding site and the binding effect of p53 on the promoter region of PHLDA1 were verified by our bioinformatics data analysis and luciferase reporter assay. Indeed, we used CRISPR-Cas9 to knockout the p53 gene in HeLa cells and further confirmed that p53 can bind to the promoter region of PHLDA1 gene, and then directly regulate the expression of PHLDA1 by recruiting P300 and CBP to change the acetylation and methylation levels in the promoter region. Finally, a series of gain-of-function experiments further confirmed that p53 re-expression in HeLa p53-/- cell can up-regulate the reduction of PHLDA1 caused by p53 knockout, and affect cell apoptosis and proliferation. Our study is the first to explore the regulatory mechanism of p53 on PHLDA1 by using the p53 gene knockout cell model, which further proves that PHLDA1 is a target-gene in p53-mediated apoptosis, and reveals the important role of PHLDA1 in cell fate determination.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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