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Updated: Jul 9, 2025

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Structural and functional insights into GSDMB isoforms complex roles in pathogenesis.

Sara Colomo1,2, David Ros-Pardo3, Sara S Oltra1,2,4

  • 1Biochemistry Department, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas 'Sols-Morreale' (IIBm-CISC), Madrid, Spain.

Cell Cycle (Georgetown, Tex.)
|December 1, 2023
PubMed
Summary

Gasdermins (GSDMs) are crucial in immunity and disease. This review details Gasdermin B (GSDMB) isoforms, revealing how alternative splicing and structure influence its role in cell death and disease.

Keywords:
Gasderminalternative splicingcancercell deathinflammatory diseasespyroptosis

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Area of Science:

  • Molecular Biology
  • Immunology
  • Cell Biology

Background:

  • Gasdermins (GSDMs) are key regulators of innate immunity, inflammation, and cell death processes like pyroptosis.
  • Gasdermin B (GSDMB) has shown conflicting roles in pyroptosis, despite its activation pathway by Granzyme A (GZMA) being known.

Purpose of the Study:

  • To review structural differences among GSDMB isoforms.
  • To investigate how structural aspects affect GZMA-mediated activation of GSDMB isoforms.
  • To elucidate the complex functions of GSDMB isoforms in disease pathogenesis and therapeutic strategies.

Main Methods:

  • Literature review of recent publications on GSDMB.
  • Analysis of structural data for crystallized GSDMB isoforms.
  • Investigation of alternative splicing's role in GSDMB isoform function.

Main Results:

  • Alternative splicing, particularly exon 6, critically determines GSDMB's pyroptotic capacity.
  • Structural variations among GSDMB isoforms influence their susceptibility to GZMA activation.
  • GSDMB isoforms exhibit diverse cell death-dependent and independent functions.

Conclusions:

  • Understanding GSDMB isoform structures and activation mechanisms is vital for clarifying its role in diseases.
  • Targeting specific GSDMB isoforms may offer novel therapeutic avenues for inflammatory diseases and cancer.