biostudies-literatureSripathy SPNCI NIH HHS6376-84https://www.ebi.ac.uk/biostudies/studies/S-EPMC4094353biostudies-literatureUnknown27(49)In the presence of ERbeta, trans-hydroxytamoxifen (TOT) protects cells against 17beta-estradiol (E(2))-induced oxidative DNA damage (ODD) and this correlates with increased expression of the antioxidative enzyme quinone reductase (QR). Here, we investigate the molecular mechanism responsible for ERbeta-mediated protection against ODD. We observe constitutive interaction between ERbeta and the novel protein hPMC2. Using a combination of breast epithelial cell lines that are either positive or negative for ERalpha, we demonstrate TOT-dependent recruitment of both ERbeta and hPMC2 to the EpRE (electrophile response element)-regulated antioxidative enzyme QR. We further demonstrate TOT-dependent corecruitment of the coactivators Nrf2, PARP-1 (poly (ADP-ribose) polymerase 1) and topoisomerase IOncogenehPMC2 is required for recruiting an ERbeta coactivator complex to mediate transcriptional upregulation of NQO1 and protection against oxidative DNA damage by tamoxifen.PMC4094353R03 CA130066CA130066CA92440R01 CA092440Gaikwad NWChaplin LJMontano MMRogan EGSripathy SPfalsehPMC2 is required for recruiting an ERbeta coactivator complex to mediate transcriptional upregulation of NQO1 and protection against oxidative DNA damage by tamoxifen.In the presence of ERbeta, trans-hydroxytamoxifen (TOT) protects cells against 17beta-estradiol (E(2))-induced oxidative DNA damage (ODD) and this correlates with increased expression of the antioxidative enzyme quinone reductase (QR). Here, we investigate the molecular mechanism responsible for ERbeta-mediated protection against ODD. We observe constitutive interaction between ERbeta and the novel protein hPMC2. Using a combination of breast epithelial cell lines that are either positive or negative for ERalpha, we demonstrate TOT-dependent recruitment of both ERbeta and hPMC2 to the EpRE (electrophile response element)-regulated antioxidative enzyme QR. We further demonstrate TOT-dependent corecruitment of the coactivators Nrf2, PARP-1 (poly (ADP-ribose) polymerase 1) and topoisomerase I2008-01-01T00:00:00Z2008 Oct2025-04-26T09:14:43.034Z2019-03-27T01:31:55ZS-EPMC40943531866336010.1038/onc.2008.235