Loss of the mono-ADP-ribosyltransferase, tiparp, increases sensitivity to dioxin-induced steatohepatitis and lethality

Abstract

Background: Tiparp is an aryl hydrocarbon receptor (AHR) repressor, but its role in dioxin toxicity is unknown. Results: Loss of Tiparp increases sensitivity to dioxin toxicity and lethality. Tiparp ADP-ribosylates AHR, which is reversed by the mono-ADP-ribosylase, MacroD1. Conclusion: We identify new roles for Tiparp, MacroD1, and ADP-ribosylation in AHR signaling and dioxin toxicity. Significance: These data reveal the importance of TIPARP in regulating AHR activity in mice.