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

Abstract

It is likely that the majority of proteins will undergo post-translational modification, be it enzymatic or non-enzymatic. These modified protein(s) regulate activity, localization and interaction with other cellular molecules thereby maintaining cellular hemostasis. Alcohol exposure significantly alters several of these post-translational modifications leading to impairments of many essential physiological processes. Here, we present new insights into novel modifications following ethanol exposure and their role in the initiation and progression of liver injury. This critical review condenses the proceedings of a symposium at the European Society for the Biomedical Research on Alcoholism Meeting held September 12-15, 2015, in Valencia, Spain.

Keywords: Acetylation; Alcohol; Betaine; Carbonylation methylation; Dysfunction; Glycosylation; Liver; Methylation; Phosphorylation; Post-translational protein modification; Sumoylation; Ubiquitination.

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.