Dioxin-dependent Activation of Murine Cyp1a-1 Gene Transcription Requires Protein Kinase C-dependent Phosphorylation

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1992 Apr 1

PMID 1312672

Citations 28

Authors

F Carrier

R A Owens

D W Nebert

A Puga

Affiliations

Soon will be listed here.

Abstract

Transcriptional activation of the murine Cyp1a-1 (cytochrome P(1)450) gene by inducers such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (dioxin) requires the aromatic hydrocarbon (Ah) receptor and the interaction of an inducer-receptor complex with one or more of the Ah-responsive elements (AhREs) located about 1 kb upstream from the transcriptional initiation site. We find that treatment of mouse hepatoma Hepa-1 cells with 2-aminopurine, an inhibitor of protein kinase activity, inhibits CYP1A1 mRNA induction by TCDD as well as the concomitant increase in CYP1A1 enzyme activity. Formation of DNA-protein complexes between the Ah receptor and its AhRE target is also inhibited by 2-aminopurine, as determined by gel mobility shift assays. Phosphorylation is required for the formation of Ah receptor-specific complexes, since in vitro dephosphorylation of nuclear extracts from TCDD-treated Hepa-1 cells abolishes the capacity of the Ah receptor to form specific complexes with its cognate AhRE sequences. To determine whether any one of several known protein kinases was involved in the transcriptional regulation of the Cyp1a-1 gene, we treated Hepa-1 cells with nine other protein kinase inhibitors prior to induction with TCDD; nuclear extracts from these cells were analyzed for their capacity to form specific DNA-protein complexes. Only extracts from cells treated with staurosporine, a protein kinase C inhibitor, were unable to form these complexes. In addition, staurosporine completely inhibited CYP1A1 mRNA induction by TCDD. Depletion of protein kinase C by prolonged treatment with phorbol ester led to the complete suppression of CYP1A1 mRNA induction by TCDD. We conclude that (i) phosphorylation is necessary for the formation of a transcriptional complex and for transcriptional activation of the Cyp1a-1 gene; (ii) the phosphorylation site(s) exists on at least one of the proteins constituting the transcriptional complex, possibly the Ah receptor itself; and (iii) the enzyme responsible for the phosphorylation is likely to be protein kinase C.

Citing Articles

The complex biology of aryl hydrocarbon receptor activation in cancer and beyond.

Opitz C, Holfelder P, Prentzell M, Trump S Biochem Pharmacol. 2023; 216:115798.

PMID: 37696456 PMC: 10570930. DOI: 10.1016/j.bcp.2023.115798.

Ah Receptor Pathway Intricacies; Signaling Through Diverse Protein Partners and DNA-Motifs.

Jackson D, Joshi A, Elferink C Toxicol Res (Camb). 2016; 4(5):1143-1158.

PMID: 26783425 PMC: 4714567. DOI: 10.1039/c4tx00236a.

Cross-talk between aryl hydrocarbon receptor and the inflammatory response: a role for nuclear factor-κB.

Vogel C, Khan E, Leung P, Gershwin M, Chang W, Wu D J Biol Chem. 2013; 289(3):1866-75.

PMID: 24302727 PMC: 3894361. DOI: 10.1074/jbc.M113.505578.

Genome-wide RNAi high-throughput screen identifies proteins necessary for the AHR-dependent induction of CYP1A1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Solaimani P, Damoiseaux R, Hankinson O Toxicol Sci. 2013; 136(1):107-19.

PMID: 23997114 PMC: 3829574. DOI: 10.1093/toxsci/kft191.

Cytochrome P450 CYP1A1: wider roles in cancer progression and prevention.

Androutsopoulos V, Tsatsakis A, Spandidos D BMC Cancer. 2009; 9:187.

PMID: 19531241 PMC: 2703651. DOI: 10.1186/1471-2407-9-187.

References

Nebert D . The Ah locus: genetic differences in toxicity, cancer, mutation, and birth defects. Crit Rev Toxicol. 1989; 20(3):153-74. DOI: 10.3109/10408448909017908. View

Durrin L, Whitlock Jr J . 2,3,7,8-Tetrachlorodibenzo-p-dioxin-inducible aryl hydrocarbon receptor-mediated change in CYP1A1 chromatin structure occurs independently of transcription. Mol Cell Biol. 1989; 9(12):5733-7. PMC: 363747. DOI: 10.1128/mcb.9.12.5733-5737.1989. View

Onoda T, Iinuma H, Sasaki Y, Hamada M, Isshiki K, Naganawa H . Isolation of a novel tyrosine kinase inhibitor, lavendustin A, from Streptomyces griseolavendus. J Nat Prod. 1989; 52(6):1252-7. DOI: 10.1021/np50066a009. View

Hershey J . Protein phosphorylation controls translation rates. J Biol Chem. 1989; 264(35):20823-6. View

Denison M, Vella L, Okey A . Ah receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat liver: lack of sensitivity to alkaline phosphatase when compared with that of glucocorticoid receptor. Arch Biochem Biophys. 1989; 273(2):458-65. DOI: 10.1016/0003-9861(89)90505-5. View

Heasley L, Johnson G . Regulation of protein kinase C by nerve growth factor, epidermal growth factor, and phorbol esters in PC12 pheochromocytoma cells. J Biol Chem. 1989; 264(15):8646-52. View

Migliaccio A, Di Domenico M, Green S, De Falco A, Kajtaniak E, Blasi F . Phosphorylation on tyrosine of in vitro synthesized human estrogen receptor activates its hormone binding. Mol Endocrinol. 1989; 3(7):1061-9. DOI: 10.1210/mend-3-7-1061. View

Durrin L, Whitlock Jr J . In situ protein-DNA interactions at a dioxin-responsive enhancer associated with the cytochrome P1-450 gene. Mol Cell Biol. 1987; 7(8):3008-11. PMC: 367925. DOI: 10.1128/mcb.7.8.3008-3011.1987. View

Denison M, Fisher J, Whitlock Jr J . The DNA recognition site for the dioxin-Ah receptor complex. Nucleotide sequence and functional analysis. J Biol Chem. 1988; 263(33):17221-4. View

10.

EDELMAN A, Blumenthal D, KREBS E . Protein serine/threonine kinases. Annu Rev Biochem. 1987; 56:567-613. DOI: 10.1146/annurev.bi.56.070187.003031. View

11.

Prochownik E, Kukowska J . Deregulated expression of c-myc by murine erythroleukaemia cells prevents differentiation. Nature. 1986; 322(6082):848-50. DOI: 10.1038/322848a0. View

12.

Sogawa K, Yamane M, Fujii-Kuriyama Y . Characterization of xenobiotic responsive elements upstream from the drug-metabolizing cytochrome P-450c gene: a similarity to glucocorticoid regulatory elements. Nucleic Acids Res. 1987; 15(10):4179-91. PMC: 340840. DOI: 10.1093/nar/15.10.4179. View

13.

Green S, Walter P, Kumar V, Krust A, Bornert J, Argos P . Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature. 1986; 320(6058):134-9. DOI: 10.1038/320134a0. View

14.

Ballester R, Rosen O . Fate of immunoprecipitable protein kinase C in GH3 cells treated with phorbol 12-myristate 13-acetate. J Biol Chem. 1985; 260(28):15194-9. View

15.

Benedict W, Gielen J, Owens I, Niwa A, Bebert D . Aryl hydrocarbon hydroxylase induction in mammalian liver cell culture. IV. Stimulation of the enzyme activity in established cell lines derived from rat or mouse hepatoma and from normal rat liver. Biochem Pharmacol. 1973; 22(21):2766-9. DOI: 10.1016/0006-2952(73)90138-x. View

16.

Bernhard H, Darlington G, Ruddle F . Expression of liver phenotypes in cultured mouse hepatoma cells: synthesis and secretion of serum albumin. Dev Biol. 1973; 35(1):83-96. DOI: 10.1016/0012-1606(73)90008-0. View

17.

Legon S, Brayley A, Hunt T, Jackson R . The effect of cyclic AMP and related compounds on the control of protein synthesis in reticulocyte lysates. Biochem Biophys Res Commun. 1974; 56(3):745-52. DOI: 10.1016/0006-291x(74)90668-8. View

18.

Nebert D, Gelboin H . Substrate-inducible microsomal aryl hydroxylase in mammalian cell culture. I. Assay and properties of induced enzyme. J Biol Chem. 1968; 243(23):6242-9. View

19.

Levy J, Teuerstein I, Marbach M, Radian S, Sharoni Y . Tyrosine protein kinase activity in the DMBA-induced rat mammary tumor: inhibition by quercetin. Biochem Biophys Res Commun. 1984; 123(3):1227-33. DOI: 10.1016/s0006-291x(84)80264-8. View

20.

Hidaka H, Inagaki M, Kawamoto S, Sasaki Y . Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C. Biochemistry. 1984; 23(21):5036-41. DOI: 10.1021/bi00316a032. View