Gasdermin-B (GSDMB) takes center stage in antibacterial defense, inflammatory diseases, and cancer

One of the hottest topics in biomedical research is to decipher the functional implications of the Gasdermin (GSDM) protein family in human pathologies. These proteins are the key effectors of a lytic and pro-inflammatory cell death type termed pyroptosis (also known as "Gasdermin-mediated prog...

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Bibliographic Details
Published in:The FEBS journal 2024-07, Vol.291 (14), p.3060-3071
Main Authors: Sarrio, David, Colomo, Sara, Moreno-Bueno, Gema
Format: Article
Language:English
Subjects:
Antiinfectives and antibacterials
Apoptosis
Biomarkers
Biomedical data
Biomedical materials
Cancer
Cell death
Functionals
Health risks
Inflammatory bowel diseases
Isoforms
Medical research
Mortality
Multitasking
Proteins
Pyroptosis
Therapeutic targets
Ulcerative colitis
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Summary:One of the hottest topics in biomedical research is to decipher the functional implications of the Gasdermin (GSDM) protein family in human pathologies. These proteins are the key effectors of a lytic and pro-inflammatory cell death type termed pyroptosis (also known as "Gasdermin-mediated programmed cell death"). However, ever-growing evidence showed that GSDMs can play multiple and complex roles in a context-dependent manner. In this sense, Gasdermin-B (GSDMB; the only GSDM gene absent in mice and rats) has been implicated in antibacterial defense, numerous inflammatory pathologies (e.g., asthma, ulcerative colitis), and cancer, but both cell death-dependent and -independent functions have been reported in these diseases, fueling the debate on whether GSDMB has genuine pyroptotic capacity. Recently, a series of seminal papers cast light on the GSDMB multitasking capacity by showing that different GSDMB transcriptional isoforms have distinct biological activities. Nonetheless, there are still obscure areas to be clarified on the precise functional involvement of GSDMB translated variants in physiological and pathological conditions. In this viewpoint, we critically discuss the most recent and exciting data on this topic and propose a series of relevant challenges that need to be overcome before GSDMB-driven biomedical applications (as a biomarker of disease risk/progression/outcome or as specific therapeutic target) become a reality in clinical settings.
ISSN:1742-464X
1742-4658
1742-4658
DOI:10.1111/febs.17018