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The mycobacterial phosphatase PtpA regulates the expression of host genes and promotes cell proliferation

Author

Listed:
  • Jing Wang

    (Chinese Academy of Sciences)

  • Pupu Ge

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Lihua Qiang

    (Chinese Academy of Sciences
    Anhui University)

  • Feng Tian

    (Peking University)

  • Dongdong Zhao

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Qiyao Chai

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Mingzhao Zhu

    (Chinese Academy of Sciences)

  • Rongbin Zhou

    (University of Science and Technology of China)

  • Guangxun Meng

    (Chinese Academy of Sciences)

  • Yoichiro Iwakura

    (Tokyo University of Science)

  • George Fu Gao

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Cui Hua Liu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

Abstract

Mycobacterium tuberculosis PtpA is a secreted effector protein that dephosphorylates several proteins in the host cell cytoplasm, such as p-JNK, p-p38, and p-VPS33B, leading to suppression of host innate immunity. Here we show that, in addition, PtpA enters the nucleus of host cells and regulates the expression of host genes, some of which are known to be involved in host innate immunity or in cell proliferation and migration (such as GADD45A). PtpA can bind directly to the promoter region of GADD45A in vitro. Both phosphatase activity and DNA-binding ability of PtpA are important in suppressing host innate immune responses. Furthermore, PtpA-expressing Mycobacterium bovis BCG promotes proliferation and migration of human lung adenoma A549 cells in vitro and in a mouse xenograft model. Further research is needed to test whether mycobacteria, via PtpA, might affect cell proliferation or migration in humans.

Suggested Citation

  • Jing Wang & Pupu Ge & Lihua Qiang & Feng Tian & Dongdong Zhao & Qiyao Chai & Mingzhao Zhu & Rongbin Zhou & Guangxun Meng & Yoichiro Iwakura & George Fu Gao & Cui Hua Liu, 2017. "The mycobacterial phosphatase PtpA regulates the expression of host genes and promotes cell proliferation," Nature Communications, Nature, vol. 8(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00279-z
    DOI: 10.1038/s41467-017-00279-z
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    Cited by:

    1. Lihua Qiang & Yong Zhang & Zehui Lei & Zhe Lu & Shasha Tan & Pupu Ge & Qiyao Chai & Mengyuan Zhao & Xinwen Zhang & Bingxi Li & Yu Pang & Lingqiang Zhang & Cui Hua Liu & Jing Wang, 2023. "A mycobacterial effector promotes ferroptosis-dependent pathogenicity and dissemination," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Mădălina Preda & Bogdan Cosmin Tănase & Daniela Luminița Zob & Adelina Silvana Gheorghe & Cristian Virgil Lungulescu & Elena Adriana Dumitrescu & Dana Lucia Stănculeanu & Loredana Sabina Cornelia Mano, 2023. "The Bidirectional Relationship between Pulmonary Tuberculosis and Lung Cancer," IJERPH, MDPI, vol. 20(2), pages 1-13, January.

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