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Controlling pyroptosis through post-translational modifications of gasdermin D

Na Zhang1, Daichao Xu2

  • 1Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China.

Developmental Cell
|April 8, 2025
PubMed

Insights

Gasdermin D (GSDMD) triggers pyroptosis and inflammation. Post-translational modifications (PTMs) regulate GSDMD activity beyond cleavage, offering insights into inflammatory diseases.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Pyroptosis is a programmed cell death pathway critical for innate immunity and inflammation.
  • Gasdermin D (GSDMD) is a key effector protein mediating pyroptosis by forming membrane pores.
  • Dysregulated pyroptosis contributes to various inflammatory pathologies.

Purpose of the Study:

  • To review the regulatory role of post-translational modifications (PTMs) in controlling Gasdermin D (GSDMD) activity.
  • To explore how PTMs link biological contexts to pyroptosis in innate immunity and inflammation.
  • To highlight potential therapeutic strategies targeting GSDMD regulation for inflammatory conditions.

Main Methods:

  • Literature review of studies investigating Gasdermin D (GSDMD) and its post-translational modifications (PTMs).
  • Analysis of research on the mechanisms by which PTMs modulate GSDMD pore formation and pyroptosis.
  • Synthesis of findings linking PTMs of GSDMD to innate immunity and inflammatory processes.

Main Results:

  • Post-translational modifications (PTMs) represent a crucial layer of regulation for Gasdermin D (GSDMD) activity, independent of proteolytic cleavage.
  • Specific PTMs influence GSDMD oligomerization, membrane insertion, and pore formation, thereby controlling pyroptosis execution.
  • Understanding PTMs of GSDMD provides insights into the fine-tuning of inflammatory responses.

Conclusions:

  • Post-translational modifications (PTMs) are critical regulators of Gasdermin D (GSDMD) function in pyroptosis and inflammation.
  • Targeting GSDMD PTMs offers promising avenues for developing novel therapeutics for inflammatory diseases.
  • Further research into GSDMD PTMs will enhance our understanding of innate immunity and pathology.
Keywords:
GSDMDgasderminpalmitoylationphosphorylationpore formingpost-translational modificationpyroptosisubiquitination

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