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Title: Human glutathione S-transferase P1-1 functions as an estrogen receptor α signaling modulator

Highlights: • GSTP induces the classical ERα signaling event. • The functional GSTP is a prerequisite for GSTP-induced ERα transcription activity. • The expression of RIP140, a transcription cofactor, was inhibited by GSTP protein. • We propose the novel non-enzymatic role of GSTP. - 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 themore » 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.« less
Authors:
 [1] ;  [2] ; ;  [1] ;  [3] ;  [4]
  1. Department of Biological Science, Sookmyung Women’s University, Seoul (Korea, Republic of)
  2. Department of Food and Nutrition, College of Life Science, Sookmyung Women’s University, Seoul (Korea, Republic of)
  3. Department of Pharmacy, College of Pharmacy, Sookmyung Women’s University, Seoul (Korea, Republic of)
  4. Department of Medical and Pharmaceutical Science, College of Science, Sookmyung Women’s University, Seoul (Korea, Republic of)
Publication Date:
OSTI Identifier:
22416762
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 452; Journal Issue: 3; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CHEMOTHERAPY; DMSO; ENZYMES; ESTROGENS; FLUORINATED ALIPHATIC HYDROCARBONS; GLUTATHIONE; HUMAN POPULATIONS; IMMUNOGLOBULINS; LIGANDS; MAMMARY GLANDS; MESSENGER-RNA; METABOLISM; NEOPLASMS; POLYVINYLS; RECEPTORS; TRANSCRIPTION; TRANSCRIPTION FACTORS