Affiliation:
1. Biochemistry Department Instituto de Investigaciones Biomédicas “Alberto Sols” (IIBm‐CISC), Conexión Cáncer (UAM‐CSIC), Universidad Autónoma de Madrid (UAM) Spain
2. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) Instituto de Salud Carlos III Madrid Spain
3. Fundación MD Anderson Internacional Madrid Spain
Abstract
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.
Funder
Fundación Científica Asociación Española Contra el Cáncer
Instituto de Salud Carlos III
Ministerio de Ciencia e Innovación
Subject
Cell Biology,Molecular Biology,Biochemistry