title: Induction of 26S proteasome subunit PSMB5 by the bifunctional inducer 3-methylcholanthrene through the Nrf2-ARE, but not the AhR/Arnt-XRE, pathway.
abstract: The 26S proteasome is responsible for degradation of abnormal intracellular proteins, including oxidatively damaged proteins and may play a role as a component of a cellular antioxidative system. However, little is known about regulation of proteasome expression. In the present study, regulation of proteasome expression by the bifunctional enzyme inducer and a specific signaling pathway for this regulation were investigated in murine neuroblastoma cells. Expression of catalytic core subunits including PSMB5 and peptidase activities of the proteasome were elevated following incubation with 3-methylcholanthrene (3-MC). Studies using reporter genes containing the murine Psmb5 promoter showed that transcriptional activity of this gene was enhanced by 3-MC. Overexpression of AhR/Arnt did not affect activation of the Pmsb5 promoter by 3-MC and deletion of the xenobiotic response elements (XREs) from this promoter exerted modest effects on inducibility in response to 3-MC. However, mutation of the proximal AREs of the Psmb5 promoter largely abrogated its inducibility by 3-MC. In addition, this promoter showed a blunted response toward 3-MC in the absence of nrf2; 3-MC incubation increased nuclear levels of Nrf2 only in wild-type cells. Collectively, these results indicate that expression of proteasome subunit PSMB5 is modulated by bifunctional enzyme inducers in a manner independent of the AhR/Arnt-XRE pathway but dependent upon the Nrf2-ARE pathway.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeonsan-si, South Korea. mkwak@yumail.ac.kr
authors.forename: Mi-Kyoung
authors.initials: MK
authors.lastname: Kwak
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Kensler
mesh_terms: D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015151:Immunoblotting; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008748:Methylcholanthrene / Q000494:pharmacology*; D009154:Mutation; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014162:Transfection; D019324:beta-Naphthoflavone / Q000494:pharmacology
chemical_list: C497397:Arnt protein, mouse; D051267:NF-E2-Related Factor 2; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011993:Recombinant Fusion Proteins; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D008748:Methylcholanthrene; D019324:beta-Naphthoflavone; D008156:Luciferases; D046988:Proteasome Endopeptidase Complex; C478802:Psmb5 protein, mouse; C061553:ATP dependent 26S protease