Aryl hydrocarbon receptor activation by dioxin targets phosphoenolpyruvate carboxykinase (PEPCK) for ADP-ribosylation via 2,3,7,8-Tetrachlorodibenzo-p- dioxin (TCDD)-inducible poly(ADP-ribose) polymerase (TiPARP) Academic Article uri icon

Overview

MeSH Major

  • Adenosine Diphosphate Ribose
  • Phosphoenolpyruvate Carboxykinase (ATP)
  • Poly(ADP-ribose) Polymerases
  • Polychlorinated Dibenzodioxins
  • Receptors, Aryl Hydrocarbon

abstract

  • Effects of the environmental toxin and carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) include a wasting syndrome associated with decreased gluconeogenesis. TCDD is a potent activator of the aryl hydrocarbon receptor (AHR), a ligand activated transcription factor. The relationship between gene activation by the AHR and TCDD toxicities is not well understood. We recently identified a pathway by which the AHR target gene TiPARP (TCDD-inducible poly(ADP-ribose) polymerase) contributes to TCDD suppression of transcription of phosphoenolpyruvate carboxykinase (PEPCK), a key regulator of gluconeogenesis, by consuming NAD(+) and decreasing Sirtuin 1 activation of the peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α), a transcriptional activator of PEPCK. We report here that TCDD-induced TiPARP also targets PEPCK for ADP-ribosylation. Both cytosolic and mitochondrial forms of PEPCK were found to undergo ADP-ribosylation. Unexpectedly, AHR suppression also enhanced ADP-ribosylation and did so by a poly(ADP-ribose) polymerase-independent mechanism. This report 1) identifies ADP-ribosylation as a new posttranslational modification for PEPCK, 2) describes a pathway by which transcriptional induction of TiPARP by the AHR can lead to a downstream posttranslational change in a TCDD target protein (PEPCK), and 3) reveals that the AHR exerts complex, previously unidentified modulatory effects on ADP-ribosylation.

publication date

  • July 26, 2013

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3724612

Digital Object Identifier (DOI)

  • 10.1074/jbc.M113.458067

PubMed ID

  • 23770670

Additional Document Info

start page

  • 21514

end page

  • 25

volume

  • 288

number

  • 30