Fas/CD95 Signaling Pathway in Damage-Associated Molecular Pattern (DAMP)-Sensing Receptors

Study of the initial steps of the CD95-mediated signaling pathways is a field of intense research and a long list of actors has been described in the literature. Nonetheless, the dynamism of protein-protein interactions (PPIs) occurring in the presence or absence of its natural ligand, CD95L, and the cellular distribution where these PPIs take place render it difficult to predict what will be the cellular outcome associated with the receptor engagement. Accordingly, CD95 stimulation can trigger apoptosis, necroptosis, pyroptosis, or pro-inflammatory signaling pathways such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) and phosphatidylinositol-3-kinase (PI3K). Recent data suggest that CD95 can also activate pattern recognition receptors (PRRs) known to sense damage-associated molecular patterns (DAMPs) such as DNA debris and dead cells. This activation might contribute to the pro-inflammatory role of CD95 and favor cancer development or severity of chronic inflammatory and auto-immune disorders. Herein, we discuss some of the molecular links that might connect the CD95 signaling to DAMP sensors.

Automated summary

The study of CD95-mediated signaling pathways is significant, and previous research has identified numerous factors involved. However, due to the dynamic nature of protein-protein interactions and their occurring in various cellular locations, it is difficult to predict the specific cellular outcomes associated with CD95 engagement. CD95 stimulation can lead to apoptosis, necroptosis, pyroptosis, or pro-inflammatory signaling pathways. Recent data suggests that CD95 may also activate pattern recognition receptors that sense damage-associated molecular patterns, potentially contributing to inflammation and cancer development or severity of chronic inflammatory and autoimmune disorders.