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Induction and superinduction of 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible ioly(ADP-ribose) polymerase: role of the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator transcription activation domains and a labile transcription repressor.

Authors
Ma-Q
Source
Arch Biochem Biophys 2002 Aug; 404(2):309-316
NIOSHTIC No.
20022859
Abstract
The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces a novel poly(ADP-ribose) polymerase (TiPARP). In this study, the signaling pathway of the induction was analyzed. Induction of TiPARP by TCDD occurs in both hepa1c1c7 cells and C57 mouse liver. Induction is concentration and time dependent. Genetic analyses reveal that induction is abolished in aromatic hydrocarbon receptor (AhR)- or aromatic hydrocarbon receptor nuclear translocator (Arnt)-defective variants but restored upon reconstitution of the variant cells with cDNAs expressing functional AhR or Arnt. Moreover, induction is largely reduced in cells expressing a deletion mutant of AhR or Arnt lacking the transcription activation (TA) domain, thus implicating the TA activities of both AhR and Arnt in the induction. Inhibition of protein synthesis by cycloheximide enhances the induction of TiPARP in the presence of an AhR agonist. The superinduction is transcriptional and does not require pretreatment with TCDD. Finally, inhibition of the 26S proteasomes by MG132 superinduces TiPARP. These findings establish that induction of TiPARP by TCDD is mediated through an AhR and Arnt transcription activation-dependent signal transduction that is repressed by a labile factor through the ubiquitin–26S proteasome-mediated protein degradation.
Keywords
Environmental-contamination; Genetic-factors; Liver-tissue; Animals; Animal-studies; Laboratory-animals; Dioxins; Aromatic-hydrocarbons; Hydrocarbons
CODEN
ABBIA4
CAS No.
1746-01-6
Publication Date
20020801
Document Type
Journal Article
Email Address
qam1@cdc.gov
Fiscal Year
2002
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
0003-9861
NIOSH Division
HELD
Source Name
Archives of Biochemistry and Biophysics
State
WV
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