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SUMO1 modification of PTEN regulates tumorigenesis by controlling its association with the plasma membrane

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  • Jian Huang

    (Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine (SJTU-SM)
    Laboratory of Tumor Suppressor Genes and MiRNAs, Institute of Medical Science, Shanghai Jiao Tong University School of Medicine (SJTU-SM))

  • Jie Yan

    (Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine (SJTU-SM)
    Laboratory of Tumor Suppressor Genes and MiRNAs, Institute of Medical Science, Shanghai Jiao Tong University School of Medicine (SJTU-SM))

  • Jian Zhang

    (Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM))

  • Shiguo Zhu

    (Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine (SJTU-SM))

  • Yanli Wang

    (Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine (SJTU-SM)
    Laboratory of Tumor Suppressor Genes and MiRNAs, Institute of Medical Science, Shanghai Jiao Tong University School of Medicine (SJTU-SM))

  • Ting Shi

    (Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM))

  • Changhong Zhu

    (Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine (SJTU-SM)
    Laboratory of Tumor Suppressor Genes and MiRNAs, Institute of Medical Science, Shanghai Jiao Tong University School of Medicine (SJTU-SM))

  • Cheng Chen

    (Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine (SJTU-SM)
    Laboratory of Tumor Suppressor Genes and MiRNAs, Institute of Medical Science, Shanghai Jiao Tong University School of Medicine (SJTU-SM))

  • Xin Liu

    (Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine (SJTU-SM)
    Laboratory of Tumor Suppressor Genes and MiRNAs, Institute of Medical Science, Shanghai Jiao Tong University School of Medicine (SJTU-SM))

  • Jinke Cheng

    (Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine (SJTU-SM))

  • Tomas Mustelin

    (Infectious and Inflammatory Disease Center, Sanford-Burnham Medical Research Institute)

  • Gen-Sheng Feng

    (University of California San Diego)

  • Guoqiang Chen

    (Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM))

  • Jianxiu Yu

    (Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine (SJTU-SM)
    Laboratory of Tumor Suppressor Genes and MiRNAs, Institute of Medical Science, Shanghai Jiao Tong University School of Medicine (SJTU-SM)
    Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM))

Abstract

The membrane association of the tumour suppressor phosphatase and tensin homologue (PTEN) is required to oppose the phosphatidylinositol-3-kinase/AKT pathway by dephosphorylation of phosphatidylinositol-3,4,5-triphosphate (PIP3). How cytosolic PTEN interacts with its main substrate, PIP3, localized at the inner face of plasma membrane remains unclear. Here we show that PTEN is covalently modified by SUMO1 at both K266 and K254 sites in the C2 domain of PTEN. SUMO1 modification at K266 located in the CBR3 loop, which has a central role in PTEN membrane association, mainly facilitates cooperative binding of PTEN to the plasma membrane by electrostatic interactions. This results in the downregulation of the phosphatidylinositol-3 kinase/AKT pathway and consequently, suppression of anchorage-independent cell proliferation and tumour growth in vivo. Our data demonstrate a molecular mechanism whereby SUMO1 modification is required for PTEN tumour suppressor function by controlling PTEN membrane association and regulation of the phosphatidylinositol-3 kinase/AKT pathway.

Suggested Citation

  • Jian Huang & Jie Yan & Jian Zhang & Shiguo Zhu & Yanli Wang & Ting Shi & Changhong Zhu & Cheng Chen & Xin Liu & Jinke Cheng & Tomas Mustelin & Gen-Sheng Feng & Guoqiang Chen & Jianxiu Yu, 2012. "SUMO1 modification of PTEN regulates tumorigenesis by controlling its association with the plasma membrane," Nature Communications, Nature, vol. 3(1), pages 1-12, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1919
    DOI: 10.1038/ncomms1919
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