Fig. 3: The role of JAK-STAT signaling pathway in ferroptosis.
From: The interaction between ferroptosis and inflammatory signaling pathways
Cytokines, such as IL-6 and TNF bind to their corresponding receptors and thus induce the phosphorylation and activation of JAKs. In turn, activated JAKs phosphorylate STATs and induce their dimerization and nuclear translocation. Finally, STAT dimers bind to DNA sequences to induce the transcription of target genes and the activation of downstream signaling pathways. As a downstream target of the JAK-STAT pathway, phosphorylated STAT3 can increase hepcidin expression to inhibit iron export, resulting in ferroptosis. Moreover, activated STAT1 inhibits System Xc- and exerts proferroptosis effects by via modulating IRF1.
