P55PIK Regulates P53-Dependent Apoptosis in Cancer Cells by Interacting with P53 DNA-Specific Domain

被引：2
|
作者：
Li, Chaoxing [1 ]
Li, Wenwen [2 ]
Cheng, Xiyao [1 ]
Zhang, Dapeng [2 ]
Sun, Xiang [1 ]
Zhou, Jingjing [1 ]
Zhou, Yin [1 ]
Huang, Yongqi [1 ]
Xia, Xianmin [1 ]
Ma, Qi [2 ,3 ]
Su, Zhengding [1 ]
机构：
[1] Hubei Univ Technol, Natl Ctr Cellular Regulat & Mol Pharmaceut 111, Hubei Key Lab Ind Microbiol, Key Lab Ind Fermentat,Minist Educ, Wuhan 430068, Peoples R China
[2] Peking Univ, State Key Lab Membrane Biol, Beijing Key Lab Cardiometab Mol Med, Peking Tsinghua Ctr Life Sci,Inst Mol Med, Beijing 100871, Peoples R China
[3] PKU Nanjing Joint Inst Translat Med, Dept Drug Discovery, Nanjing 211800, Peoples R China
来源：
ONCOTARGETS AND THERAPY | 2020年 / 13卷
基金：
中国国家自然科学基金;
关键词：
N24; p55PIK; p53; cancer; apoptosis; PHOSPHATIDYLINOSITOL; 3-KINASE; PHOSPHOINOSITIDE; PI3K PATHWAY; AMINO-ACIDS; SUBUNIT; EXPRESSION; PTEN; MECHANISMS; RELEASE; MDM2;
D O I：
10.2147/OTT.S247200
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
Purpose: Phosphatidylinositol 3-kinase (PI3K) plays an important role in tumorigenesis by cross-talking with several signaling pathways. p55PIK is a unique regulatory subunit of PI3K and contains an extra 24-residue N-terminal domain (N24). This study aimed to explore the interaction of p55PIK with p53 and the role of p55PIK in regulating p53-dependent apoptosis in cancer cells. Materials and Methods: The expression of p55PIK was detected in cancer cells, and the interaction of p55PIK with p53 was examined by immunoprecipitation and pull-down assay. The expression of p53-dependent apoptosis-related genes was detected by PCR. Results: N24 domain of p55PIK interacted with DNA-specific binding domain (DBD) of p53. The increase or decrease of p55PIK expression led to the change of the expression of p53 and p53-regulated genes in cancer cells. Moreover, N24 peptide led to the change of the expression of p53-regulated genes. Moreover, a membrane-permeable N24 peptide enhanced p53-dependent apoptosis induced by methyl methanesulfonate. Conclusion: Our results reveal a novel mechanism that regulates p53-dependent apoptosis in cancer cells via p55PIK-p53 interaction.
引用
收藏
页码：5177 / 5190
页数：14
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