title: Human glutathione S-transferase P1-1 functions as an estrogen receptor α signaling modulator.
abstract: Estrogen receptor α (ERα) plays a crucial role in estrogen-mediated signaling pathways and exerts its action as a nuclear transcription factor. Binding of the ligand-activated ERα to the estrogen response element (ERE) is a central part of ERα-associated signal transduction pathways and its aberrant modulation is associated with many disease conditions. Human glutathione S-transferase P1-1 (GSTP) functions as an enzyme in conjugation reactions in drug metabolism and as a regulator of kinase signaling pathways. It is overexpressed in tumors following chemotherapy and has been associated with a poor prognosis in breast cancer. In this study, a novel regulatory function of GSTP has been proposed in which GSTP modulates ERE-mediated ERα signaling events. Ectopic expression of GSTP was able to induce the ERα and ERE-mediated transcriptional activities in ERα-positive but GSTP-negative MCF7 human breast cancer cells. This inductive effect of GSTP on the ERE-transcription activity was diminished when the cells express a mutated form of the enzyme or are treated with a GSTP-specific chemical inhibitor. It was found that GSTP inhibited the expression of the receptor interacting protein 140 (RIP140), a negative regulator of ERα transcription, at both mRNA and protein levels. Our study suggests a novel non-enzymatic role of GSTP which plays a significant role in regulating the classical ERα signaling pathways via modification of transcription cofactors such as RIP140.
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Xiyuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Food and Nutrition, College of Life Science, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Byoung Ha
authors.initials: BH
authors.lastname: An
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Pharmacy, College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Young Sook
authors.initials: YS
authors.lastname: Kang
authors.affiliation: Department of Medical and Pharmaceutical Science, College of Science, Sookmyung Women's University, Seoul, Republic of Korea. Electronic address: minsunchang@sm.ac.kr.
authors.forename: Minsun
authors.initials: M
authors.lastname: Chang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004958:Estradiol / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D051549:Glutathione S-Transferase pi / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D000078723:Nuclear Receptor Interacting Protein 1; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020218:Response Elements; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C506487:ESR1 protein, human; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; C000627127:NRIP1 protein, human; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D012333:RNA, Messenger; D004958:Estradiol; D008156:Luciferases; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi
keywords: Breast cancer; Estrogen receptor α; Estrogen response element; Glutathione S-transferase P1-1; Regulatory interacting protein 140