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

被引：1
|
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
相关论文
共 50 条
  • [1] Suppression of Glucosylceramide Synthase Restores p53-Dependent Apoptosis in Mutant p53 Cancer Cells
    Liu, Yong-Yu
    Patwardhan, Gauri A.
    Bhinge, Kaustubh
    Gupta, Vineet
    Gu, Xin
    Jazwinski, S. Michal
    [J]. CANCER RESEARCH, 2011, 71 (06) : 2276 - 2285
  • [2] p53RDL1 regulates p53-dependent apoptosis
    Tanikawa, C
    Matsuda, K
    Fukuda, S
    Nakamura, Y
    Arakawa, H
    [J]. NATURE CELL BIOLOGY, 2003, 5 (03) : 216 - 223
  • [3] p53RDL1 regulates p53-dependent apoptosis
    Chizu Tanikawa
    Koichi Matsuda
    Seisuke Fukuda
    Yusuke Nakamura
    Hirofumi Arakawa
    [J]. Nature Cell Biology, 2003, 5 : 216 - 223
  • [4] Loss of LZAP inactivates p53 and regulates sensitivity of cells to DNA damage in a p53-dependent manner
    Wamsley, J. J.
    Gary, C.
    Biktasova, A.
    Hajek, M.
    Bellinger, G.
    Virk, R.
    Issaeva, N.
    Yarbrough, W. G.
    [J]. ONCOGENESIS, 2017, 6 : e314 - e314
  • [5] Loss of LZAP inactivates p53 and regulates sensitivity of cells to DNA damage in a p53-dependent manner
    J J Wamsley
    C Gary
    A Biktasova
    M Hajek
    G Bellinger
    R Virk
    N Issaeva
    W G Yarbrough
    [J]. Oncogenesis, 2017, 6 : e314 - e314
  • [6] p53 transcriptional activity is essential for p53-dependent apoptosis following DNA damage
    Chao, C
    Saito, S
    Kang, J
    Anderson, CW
    Appella, E
    Xu, Y
    [J]. EMBO JOURNAL, 2000, 19 (18): : 4967 - 4975
  • [7] Restoration by glycerol of p53-dependent apoptosis in cells bearing the mutant p53 gene
    Ohnishi, T
    Matsumoto, H
    Wang, X
    Takahashi, A
    Tamamoto, T
    Ohnishi, K
    [J]. INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 1999, 75 (09) : 1095 - 1098
  • [8] p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis
    Okamura, S
    Arakawa, H
    Tanaka, T
    Nakanishi, H
    Ng, CC
    Taya, Y
    Monden, M
    Nakamura, Y
    [J]. MOLECULAR CELL, 2001, 8 (01) : 85 - 94
  • [9] P53-DEPENDENT APOPTOSIS IN-VIVO - IMPACT OF P53 INACTIVATION ON TUMORIGENESIS
    SYMONDS, H
    KRALL, L
    REMINGTON, L
    ROBLES, MS
    JACKS, T
    VANDYKE, T
    [J]. COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY, 1994, 59 : 247 - 257
  • [10] p53 target gene AEN is a nuclear exonuclease required for p53-dependent apoptosis
    T Kawase
    H Ichikawa
    T Ohta
    N Nozaki
    F Tashiro
    R Ohki
    Y Taya
    [J]. Oncogene, 2008, 27 : 3797 - 3810
12345