Unfolded protein response is activated by single application of BMP-2
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BioMed Central
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Meeting abstract
Unfolded protein response is activated by single application of BMP-2 S Steinert*1, T Kroll1, I Taubert1, L Pusch1, P Hortschansky2, K Höffken1, S Wölfl3 and J Clement1 Address: 1Department of Internal Medicine II, Friedrich Schiller University Jena, Jena, Germany, 2Molecular and Applied Microbiology, HKI, Jena, Germany and 3Institute for Pharmacy and Molecular Biotechnology, University of Heidelberg, Heidelberg, Germany * Corresponding author
from 12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes Weimar, Germany. 29–31 October 2008 Published: 26 February 2009 Cell Communication and Signaling 2009, 7(Suppl 1):A37
doi:10.1186/1478-811X-7-S1-A37
12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes
Frank Entschladen, Karlheinz Friedrich, Ralf Hass and Ottmar Janssen Meeting abstracts – A single PDF containing all abstracts in this Supplement is available here.This abstract is available from: http://www.biosignaling.com/content/7/S1/A37 © 2009 Steinert et al; licensee BioMed Central Ltd.
Introduction
Results
Tumor formation and progression is characterized by a proceeding degeneration of genetic material. As a consequence a growing number of proteins are misfolded and thus accumulate in the lumen of the endoplasmic reticulum and induce the "unfolded protein response" (UPR). Activation of the UPR can cause elimination of cells through apoptosis or a restabilization and therefore cell survival.
Incubation of MCF-7 cells with BMP-2 induces a 2-fold induction of PKR expression after 24 h independent of the amount of BMP-2 applied. The alterations of PKR expression found on the mRNA level were further investigated on the protein level by western blot analysis. We could show that the BMP-2 dependent up-regulation of PKR mRNA is paralleled by an increase in PKR protein content with a subsequent down-regulation of the total protein content of PKR after 24 hours. Incubation of MCF-7 cells with BMP-2 led to a robust increase of the fraction of phosphorylated PKR after 4 hours suggesting an additional route of BMP-2 dependent regulation of PKR activation. A prominent substrate of PKR is the alpha-subunit of the translation factor eIF2. Phosphorylation of eIF2alpha leads to an inhibition of translation. During incubation of MCF-7 cells with BMP-2 the level of total eIF2alpha is not altered. In contrast, the amount of phosphorylated eIF2alpha is increased in BMP-2 treated MCF7 cells after 16 h up to 24 h. compared to serum-free controls. Cell cycle analysis revealed a slight reduction of apoptotic cells under the influence of BMP-2 in comparison to controls.
We could previously show that chronic and single application of BMP-2 alters distinct subsets of genes in the breast cancer cell line MCF-7. The group of apoptosisrelated genes was predominantly regulated after shortterm application of BMP-2. The protein kinase R (PKR) exhibited the most prom
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