NDLI: Gene regulatory network of unfolded protein response genes in endoplasmic reticulum stress

Content Provider	Springer Nature Link
Author	Takayanagi, Sayuri Fukuda, Riga Takeuchi, Yuuki Tsukada, Sakiko Yoshida, Kenichi
Copyright Year	2012
Abstract	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.
Starting Page	11
Ending Page	23
Page Count	13
File Format	PDF
ISSN	13558145
Journal	Cell Stress and Chaperones
Volume Number	18
Issue Number	1
e-ISSN	14661268
Language	English
Publisher	Springer Netherlands
Publisher Date	2012-07-18
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	ER stress Unfolded protein response ERSE UPRE BiP Gene regulation Neurosciences Biomedicine general Cell Biology Immunology Cancer Research Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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