OncoTargets and Therapy (Jun 2020)

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

  • Li C,
  • Li W,
  • Cheng X,
  • Zhang D,
  • Sun X,
  • Zhou J,
  • Zhou Y,
  • Huang Y,
  • Xia X,
  • Ma Q,
  • Su Z

Journal volume & issue
Vol. Volume 13
pp. 5177 – 5190

Abstract

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Chaoxing Li,1 Wenwen Li,2 Xiyao Cheng,1 Dapeng Zhang,2 Xiang Sun,1 Jingjing Zhou,1 Yin Zhou,1 Yongqi Huang,1 Xianmin Xia,1 Qi Ma,2,3 Zhengding Su1 1Key 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; 2State 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; 3Department of Drug Discovery, PKU-Nanjing Joint Institute of Translational Medicine, Nanjing 211800, People’s Republic of ChinaCorrespondence: Zhengding Su; Qi Ma Email [email protected]; [email protected]: 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.Keywords: N24, p55PIK, p53, cancer, apoptosis

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