Aberrant post-translational protein modifications in the pathogenesis of alcohol-induced liver injury

Figure 1 Acetaldehyde suppresses interferon-α signaling in hepatitis C virus -infected liver cells by impairing signal transducers and activators of transcription 1 methylation. The most downstream event in interferon (IFN)α signaling is the attachment of methylated STAT1 to DNA, interferon stimulated response element (ISRE) and gamma-interferon activated site (GAS), for activation of anti-viral interferon-stimulated genes (ISGs). Acetaldehyde suppresses STAT1 methylation, which facilitates increased STAT1 interaction with protein inhibitor of activated STAT 1 (PIAS1, a negative regulator of IFN signaling) preventing STAT1 binding to DNA. This ultimately results in reduced ISG activation and decreased induction of anti-viral proteins.