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Golgi stress induces SIRT2 to counteract Shigella infection via defatty-acylation

Author

Listed:
  • Miao Wang

    (Cornell University)

  • Yugang Zhang

    (Cornell University)

  • Garrison P. Komaniecki

    (Cornell University)

  • Xuan Lu

    (Cornell University)

  • Ji Cao

    (Cornell University)

  • Mingming Zhang

    (Cornell University
    Cornell University)

  • Tao Yu

    (Cornell University)

  • Dan Hou

    (Cornell University)

  • Nicole A. Spiegelman

    (Cornell University)

  • Ming Yang

    (Cornell University)

  • Ian R. Price

    (Cornell University)

  • Hening Lin

    (Cornell University
    Cornell University)

Abstract

Enzymes from pathogens often modulate host protein post-translational modifications (PTMs), facilitating survival and proliferation of pathogens. Shigella virulence factors IpaJ and IcsB induce proteolytic cleavage and lysine fatty acylation on host proteins, which cause Golgi stress and suppress innate immunity, respectively. However, it is unknown whether host enzymes could reverse such modifications introduced by pathogens’ virulence factors to suppress pathogenesis. Herein, we report that SIRT2, a potent lysine defatty-acylase, is upregulated by the transcription factor CREB3 under Golgi stress induced by Shigella infection. SIRT2 in turn removes the lysine fatty acylation introduced by Shigella virulence factor IcsB to enhance host innate immunity. SIRT2 knockout mice are more susceptible to Shigella infection than wildtype mice, demonstrating the importance of SIRT2 to counteract Shigella infection.

Suggested Citation

  • Miao Wang & Yugang Zhang & Garrison P. Komaniecki & Xuan Lu & Ji Cao & Mingming Zhang & Tao Yu & Dan Hou & Nicole A. Spiegelman & Ming Yang & Ian R. Price & Hening Lin, 2022. "Golgi stress induces SIRT2 to counteract Shigella infection via defatty-acylation," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32227-x
    DOI: 10.1038/s41467-022-32227-x
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    References listed on IDEAS

    as
    1. Tatsiana Kosciuk & Ian R. Price & Xiaoyu Zhang & Chengliang Zhu & Kayla N. Johnson & Shuai Zhang & Steve L. Halaby & Garrison P. Komaniecki & Min Yang & Caroline J. DeHart & Paul M. Thomas & Neil L. K, 2020. "NMT1 and NMT2 are lysine myristoyltransferases regulating the ARF6 GTPase cycle," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    2. Hong Jiang & Saba Khan & Yi Wang & Guillaume Charron & Bin He & Carlos Sebastian & Jintang Du & Ray Kim & Eva Ge & Raul Mostoslavsky & Howard C. Hang & Quan Hao & Hening Lin, 2013. "SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine," Nature, Nature, vol. 496(7443), pages 110-113, April.
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