Fig.12. Schematic representation of a model showing the role of 4-HNE in Fas-mediated signaling.
4-HNE promotes apoptosis by directly interacting with Fas resulting in the activation of down stream kinases ASK1 and JNK leading to the proteolytic cleavage of caspase3 culminating in apoptosis. On the other hand, a direct interaction of 4-HNE with Daxx facilitates its export from the nuclear compartment to cytosol where it binds to Fas and inhibits Fas-mediated apoptosis. Translocation of Daxx also leads to the activation of transcription factor HSF1 to transcribe stress responsive heat shock proteins.