Melanoma differentiation-associated protein 5 pathway

The Melanoma differentiation-associated protein 5 (MDA5) pathway is a crucial cytosolic signaling cascade involved in the innate immune response to viral infection. MDA5, a RIG-I-like receptor (RLR), detects long double-stranded RNA (dsRNA), typically produced during viral replication, and initiates signaling that leads to type I interferon production. The pathway involves MDA5 binding to dsRNA, interaction with MAVS on mitochondria, activation of TBK1 and IKKε kinases, phosphorylation and nuclear translocation of IRF3/IRF7, and induction of type I interferon gene expression. Aberrant activation is linked to autoimmunity and autoinflammation, while targeted activation shows promise in cancer therapy.

Activation of MDA5 induces tumor cell apoptosis through intrinsic pathways and sensitization toward extrinsic Fas-mediated apoptosis.