P55PIK通过与P53 DNA特异性结构域相互作用来调节癌细胞中P53依赖的细胞凋亡。
P55PIK Regulates P53-Dependent Apoptosis in Cancer Cells by Interacting with P53 DNA-Specific Domain.
作者信息
Li Chaoxing, Li Wenwen, Cheng Xiyao, Zhang Dapeng, Sun Xiang, Zhou Jingjing, Zhou Yin, Huang Yongqi, Xia Xianmin, Ma Qi, Su Zhengding
机构信息
Key Laboratory of Industrial Fermentation (Ministry of Education), Hubei Key Laboratory of Industrial Microbiology, National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, People's Republic of China.
State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Institute of Molecular Medicine, Peking University, Beijing 100871, People's Republic of China.
出版信息
Onco Targets Ther. 2020 Jun 8;13:5177-5190. doi: 10.2147/OTT.S247200. eCollection 2020.
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.
目的
磷脂酰肌醇3激酶（PI3K）通过与多种信号通路相互作用在肿瘤发生中起重要作用。p55PIK是PI3K的一个独特调节亚基，包含一个额外的24个残基的N端结构域（N24）。本研究旨在探讨p55PIK与p53的相互作用以及p55PIK在调节癌细胞中p53依赖性凋亡中的作用。
材料与方法
检测癌细胞中p55PIK的表达，并通过免疫沉淀和下拉试验检测p55PIK与p53的相互作用。通过PCR检测p53依赖性凋亡相关基因的表达。
结果
p55PIK的N24结构域与p53的DNA特异性结合结构域（DBD）相互作用。p55PIK表达的增加或减少导致癌细胞中p53和p53调节基因表达的变化。此外，N24肽导致p53调节基因表达的变化。此外，一种可穿透细胞膜的N24肽增强了甲磺酸甲酯诱导的p53依赖性凋亡。
结论
我们的结果揭示了一种通过p55PIK-p53相互作用调节癌细胞中p53依赖性凋亡的新机制。
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