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Title: Inhibin beta E is upregulated by drug-induced endoplasmic reticulum stress as a transcriptional target gene of ATF4

Abstract

Inhibins and activins are gonadal peptide hormones of the transforming growth factor-β super family with important functions in the reproductive system. By contrast, the recently identified inhibin βE subunit, primarily expressed in liver cells, appears to exert functions unrelated to the reproductive system. Previously shown downregulation of inhibin βE in hepatoma cells and anti-proliferative effects of ectopic inhibin βE overexpression indicated growth-regulatory effects of inhibin βE. We observed a selective re-expression of the inhibin βE subunit in HepG2 hepatoblastoma cells, MCF7 breast cancer cells, and HeLa cervical cancer cells under endoplasmic reticulum stress conditions induced by tunicamycin, thapsigargin, and nelfinavir. Analysis of XPB1 splicing and ATF4 activation revealed that inhibin βE re-expression was associated with induction of the endoplasmic reticulum stress reaction by these drugs. Transfection of an ATF4 expression plasmid specifically induced inhibin βE expression in HeLa cells and indicates inhibin βE as a hitherto unidentified target gene of ATF4, a key transcription factor of the endoplasmic reticulum stress response. Therefore, the inhibin βE subunit defines not only a new player but also a possible new marker for drug-induced endoplasmic reticulum stress. -- Highlights: ► Endoplasmic reticulum stress induces inhibin beta E expression. ► Inhibin beta E is regulatedmore » by the transcription factor ATF4. ► Inhibin beta E expression can be used as a marker for drug-induced ER stress.« less

Authors:
; ; ; ;
Publication Date:
OSTI Identifier:
22215949
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 264; Journal Issue: 2; Other Information: Copyright (c) 2012 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; BIOLOGICAL STRESS; DRUGS; ENDOPLASMIC RETICULUM; GENES; GROWTH FACTORS; HELA CELLS; HEPATOMAS; LIVER CELLS; PEPTIDE HORMONES; SPLICING; TRANSCRIPTION FACTORS

Citation Formats

Brüning, Ansgar, E-mail: ansgar.bruening@med.uni-muenchen.de, Matsingou, Christina, Brem, German Johannes, Rahmeh, Martina, and Mylonas, Ioannis. Inhibin beta E is upregulated by drug-induced endoplasmic reticulum stress as a transcriptional target gene of ATF4. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2012.08.011.
Brüning, Ansgar, E-mail: ansgar.bruening@med.uni-muenchen.de, Matsingou, Christina, Brem, German Johannes, Rahmeh, Martina, & Mylonas, Ioannis. Inhibin beta E is upregulated by drug-induced endoplasmic reticulum stress as a transcriptional target gene of ATF4. United States. doi:10.1016/J.TAAP.2012.08.011.
Brüning, Ansgar, E-mail: ansgar.bruening@med.uni-muenchen.de, Matsingou, Christina, Brem, German Johannes, Rahmeh, Martina, and Mylonas, Ioannis. Mon . "Inhibin beta E is upregulated by drug-induced endoplasmic reticulum stress as a transcriptional target gene of ATF4". United States. doi:10.1016/J.TAAP.2012.08.011.
@article{osti_22215949,
title = {Inhibin beta E is upregulated by drug-induced endoplasmic reticulum stress as a transcriptional target gene of ATF4},
author = {Brüning, Ansgar, E-mail: ansgar.bruening@med.uni-muenchen.de and Matsingou, Christina and Brem, German Johannes and Rahmeh, Martina and Mylonas, Ioannis},
abstractNote = {Inhibins and activins are gonadal peptide hormones of the transforming growth factor-β super family with important functions in the reproductive system. By contrast, the recently identified inhibin βE subunit, primarily expressed in liver cells, appears to exert functions unrelated to the reproductive system. Previously shown downregulation of inhibin βE in hepatoma cells and anti-proliferative effects of ectopic inhibin βE overexpression indicated growth-regulatory effects of inhibin βE. We observed a selective re-expression of the inhibin βE subunit in HepG2 hepatoblastoma cells, MCF7 breast cancer cells, and HeLa cervical cancer cells under endoplasmic reticulum stress conditions induced by tunicamycin, thapsigargin, and nelfinavir. Analysis of XPB1 splicing and ATF4 activation revealed that inhibin βE re-expression was associated with induction of the endoplasmic reticulum stress reaction by these drugs. Transfection of an ATF4 expression plasmid specifically induced inhibin βE expression in HeLa cells and indicates inhibin βE as a hitherto unidentified target gene of ATF4, a key transcription factor of the endoplasmic reticulum stress response. Therefore, the inhibin βE subunit defines not only a new player but also a possible new marker for drug-induced endoplasmic reticulum stress. -- Highlights: ► Endoplasmic reticulum stress induces inhibin beta E expression. ► Inhibin beta E is regulated by the transcription factor ATF4. ► Inhibin beta E expression can be used as a marker for drug-induced ER stress.},
doi = {10.1016/J.TAAP.2012.08.011},
journal = {Toxicology and Applied Pharmacology},
number = 2,
volume = 264,
place = {United States},
year = {Mon Oct 15 00:00:00 EDT 2012},
month = {Mon Oct 15 00:00:00 EDT 2012}
}