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ER Stress Decreases Gene Expression Of Transmembrane Protein 117 Via Activation of PKR-like ER Kinase

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A Correction to this article was published on 02 September 2023

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Abstract

Stress response is an inherent mechanism in the endoplasmic reticulum (ER). The inducers of ER cause a specific cascade of reactions, leading to gene expression. Transmembrane protein 117 (TMEM117) is in the ER and plasma membrane. In our previous study, TMEM117 protein expression was found to be decreased by an ER stress inducer. However, the mechanism underlying this decrease in TMEM117 protein expression remains unclear. This study aimed to elucidate the mechanism underlying the decrease in TMEM117 protein expression during ER stress and identify the unfolded protein response (UPR) pathway related to decreased TMEM117 protein expression. We showed that the gene expression levels of TMEM117 were decreased by ER stress inducers and were regulated by PKR-like ER kinase (PERK), indicating that TMEM117 protein expression was regulated by the signaling pathway. Surprisingly, gene knockdown of activating transcription factor 4 (ATF4) downstream of PERK did not affect the gene expression of TMEM117. These results suggest that TMEM117 protein expression during ER stress is transcriptionally regulated by PERK but not by ATF4. TMEM117 has a potential to be a new therapeutic target against ER stress-related diseases.

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Acknowledgements

We would like to thank Dr. Kazutoshi Mori (Kyoto University) for providing a luciferase expression plasmid for the human bip gene promoter, and Hideaki Watanabe for initial assistance in performing the experiments.

Funding

This research was supported by Tokyo University of Technology.

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Authors and Affiliations

  1. Graduate School of Bionics, Tokyo University of Technology, 1401-1 Katakura-machi, Hachioji, Tokyo, 192-0982, Japan

    Ryuto Maruyama & Tomoyasu Sugiyama

  2. Department of Life Science, Rikkyo University, 3-34-1 Nishi-Ikebukuro, Toshima-ku, Tokyo, 171-8501, Japan

    Ryuto Maruyama

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Contributions

Individual contributions are provided as follows: Conceptualization, R.M. and T.S.; methodology, R.M.; validation, R.M.; formal analysis, R.M.; investigation, R.M.; resources, R.M. and T.S.; data curation, R.M. and T.S.; writing-original draft preparation, R.M. and T.S.; writing-review and editing, R.M. and T.S.; visualization, R.M. and T.S.; supervision, R.M. and T.S.; project administration, R.M.; and funding acquisition, R.M. and T.S.. All the authors have read and agreed to the published version of the paper.

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Correspondence to Ryuto Maruyama.

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Maruyama, R., Sugiyama, T. ER Stress Decreases Gene Expression Of Transmembrane Protein 117 Via Activation of PKR-like ER Kinase. Cell Biochem Biophys 81, 459–468 (2023). https://doi.org/10.1007/s12013-023-01150-3

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