naa a22 4500 510745822 CHVBK 20180411083045.0 cr unu---uuuuu 180411e20130101xx s 000 0 eng 10.1007/s12192-012-0351-5 doi (NATIONALLICENCE)springer-10.1007/s12192-012-0351-5 Gene regulatory network of unfolded protein response genes in endoplasmic reticulum stress [Elektronische Daten] [Sayuri Takayanagi, Riga Fukuda, Yuuki Takeuchi, Sakiko Tsukada, Kenichi Yoshida] In the endoplasmic reticulum (ER), secretory and membrane proteins are properly folded and modified, and the failure of these processes leads to ER stress. At the same time, unfolded protein response (UPR) genes are activated to maintain homeostasis. Despite the thorough characterization of the individual gene regulation of UPR genes to date, further investigation of the mutual regulation among UPR genes is required to understand the complex mechanism underlying the ER stress response. In this study, we aimed to reveal a gene regulatory network formed by UPR genes, including immunoglobulin heavy chain-binding protein (BiP), X-box binding protein 1 (XBP1), C/EBP [CCAAT/enhancer-binding protein]-homologous protein (CHOP), PKR-like endoplasmic reticulum kinase (PERK), inositol-requiring 1 (IRE1), activating transcription factor 6 (ATF6), and ATF4. For this purpose, we focused on promoter-luciferase reporters for BiP, XBP1, and CHOP genes, which bear an ER stress response element (ERSE), and p5 × ATF6-GL3, which bears an unfolded protein response element (UPRE). We demonstrated that the luciferase activities of the BiP and CHOP promoters were upregulated by all the UPR genes, whereas those of the XBP1 promoter and p5 × ATF6-GL3 were upregulated by all the UPR genes except for BiP, CHOP, and ATF4 in HeLa cells. Therefore, an ERSE- and UPRE-centered gene regulatory network of UPR genes could be responsible for the robustness of the ER stress response. Finally, we revealed that BiP protein was degraded when cells were treated with DNA-damaging reagents, such as etoposide and doxorubicin; this finding suggests that the expression level of BiP is tightly regulated at the post-translational level, rather than at the transcriptional level, in the presence of DNA damage. Cell Stress Society International, 2012 ER stress nationallicence Unfolded protein response nationallicence ERSE nationallicence UPRE nationallicence BiP nationallicence Gene regulation nationallicence ATF : Activating transcription factor nationallicence BiP : Immunoglobulin heavy chain-binding protein nationallicence CHOP : C/EBP [CCAAT/enhancer-binding protein]-homologous protein nationallicence DMSO : Dimethyl sulfoxide nationallicence PDI : Protein disulfide isomerase nationallicence ER : Endoplasmic reticulum nationallicence ERAD : ER-associated degradation nationallicence ERSE : ER stress response element nationallicence 5-FU : 5-fluorouracil nationallicence GAPDH : Glyceraldehyde-3-phosphate dehydrogenase nationallicence IRE1 : Inositol-requiring 1 nationallicence PCR : Polymerase chain reaction nationallicence PERK : PKR-like endoplasmic reticulum kinase nationallicence RNAi : RNA interference nationallicence RT : Reverse transcription nationallicence siRNA : Short interference RNA nationallicence UPR : Unfolded protein response nationallicence UPRE : Unfolded protein response element nationallicence XBP1 : X-box binding protein 1 nationallicence Takayanagi Sayuri Department of Life Sciences, Meiji University, 1-1-1 Higashimita, Tama-ku, 214-8571, Kawasaki, Kanagawa, Japan aut Fukuda Riga Department of Life Sciences, Meiji University, 1-1-1 Higashimita, Tama-ku, 214-8571, Kawasaki, Kanagawa, Japan aut Takeuchi Yuuki Department of Life Sciences, Meiji University, 1-1-1 Higashimita, Tama-ku, 214-8571, Kawasaki, Kanagawa, Japan aut Tsukada Sakiko Department of Life Sciences, Meiji University, 1-1-1 Higashimita, Tama-ku, 214-8571, Kawasaki, Kanagawa, Japan aut Yoshida Kenichi Department of Life Sciences, Meiji University, 1-1-1 Higashimita, Tama-ku, 214-8571, Kawasaki, Kanagawa, Japan aut Cell Stress and Chaperones Springer Netherlands 18/1(2013-01-01), 11-23 1355-8145 18:1<11 2013 18 12192 https://doi.org/10.1007/s12192-012-0351-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12192-012-0351-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Takayanagi Sayuri Department of Life Sciences, Meiji University, 1-1-1 Higashimita, Tama-ku, 214-8571, Kawasaki, Kanagawa, Japan aut NATIONALLICENCE 700 1- Fukuda Riga Department of Life Sciences, Meiji University, 1-1-1 Higashimita, Tama-ku, 214-8571, Kawasaki, Kanagawa, Japan aut NATIONALLICENCE 700 1- Takeuchi Yuuki Department of Life Sciences, Meiji University, 1-1-1 Higashimita, Tama-ku, 214-8571, Kawasaki, Kanagawa, Japan aut NATIONALLICENCE 700 1- Tsukada Sakiko Department of Life Sciences, Meiji University, 1-1-1 Higashimita, Tama-ku, 214-8571, Kawasaki, Kanagawa, Japan aut NATIONALLICENCE 700 1- Yoshida Kenichi Department of Life Sciences, Meiji University, 1-1-1 Higashimita, Tama-ku, 214-8571, Kawasaki, Kanagawa, Japan aut NATIONALLICENCE 773 0- Cell Stress and Chaperones Springer Netherlands 18/1(2013-01-01), 11-23 1355-8145 18:1<11 2013 18 12192 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer