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Transcriptional regulation of the ER stress-inducible gene Sec16B in Neuro2a cells

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Abstract

Endoplasmic reticulum (ER) stress responses have been demonstrated to play important roles in maintaining various cellular functions and to underlie many tissue dysfunctions. In this study, we identified Sec16B as an ER stress-inducible gene by microarray analysis of brefeldin A (BFA)-inducible genes in a mouse neuroblastoma cell-line, Neuro2a. Sec16B mRNA was induced by treatment with the ER stress-inducing reagents thapsigargin (Tg) and brefeldin A in a time-dependent manner. In the genomic sequence of the mouse Sec16B gene, we found an unfolded protein response element (UPRE), which is well conserved between humans and mice. Using luciferase reporter analyses, we showed that the UPRE in the mouse Sec16B gene was functional and responded well to ER stress-inducing stimuli and spliced XBP1 (sXBP1)-overexpression. In addition, a unique ATF4-responsive sequence within the first intron of the mouse Sec16B gene was characterized. Our study may help to elucidate the regulation of trafficking through the ER–Golgi apparatus and the biogenesis of ER-derived intracellular organelles.

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Abbreviations

ATF4:

Activating transcription factor 4

ATF6:

Activating transcription factor 6

ER:

Endoplasmic reticulum

GADD153:

Growth arrest and DNA damage inducible gene 153

GRP78:

78 kDa glucose-regulated protein

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

IRE1:

Inositol-requiring enzyme-1

PERK:

PKR-like endoplasmic reticulum kinase

XBP1:

X-box binding protein 1

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Acknowledgements

This work is, in part, supported by Grant-in-aid from the Japan Society for the Promotion of Science (JSPS, Japan, KAKENHI, Nos. 17K19901 and 19H04030 to K.O.).

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Authors and Affiliations

  1. United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan

    Kentaro Oh-hashi & Yoko Hirata

  2. Graduate School of Natural Science and Technology, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan

    Kentaro Oh-hashi, Hiroki Kohno & Yoko Hirata

  3. Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan

    Kentaro Oh-hashi & Yoko Hirata

Authors
  1. Kentaro Oh-hashi
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  2. Hiroki Kohno
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  3. Yoko Hirata
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KO and HK discussed and designed the research; KO and HK performed experiments; KO and YH wrote the manuscript.

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Correspondence to Kentaro Oh-hashi.

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Oh-hashi, K., Kohno, H. & Hirata, Y. Transcriptional regulation of the ER stress-inducible gene Sec16B in Neuro2a cells. Mol Cell Biochem 476, 35–44 (2021). https://doi.org/10.1007/s11010-020-03883-8

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  • DOI: https://doi.org/10.1007/s11010-020-03883-8

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