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ERp29 deficiency affects sensitivity to apoptosis via impairment of the ATF6–CHOP pathway of stress response

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Abstract

Endoplasmic reticulum protein 29 (ERp29) belongs to the redox-inactive PDI-Dβ-subfamily of PDI-proteins. ERp29 is expressed in all mammalian tissues examined. Especially high levels of expression were observed in secretory tissues and in some tumors. However, the biological role of ERp29 remains unclear. In the present study we show, by using thyrocytes and primary dermal fibroblasts from adult ERp29−/− mice, that ERp29 deficiency affects the activation of the ATF6–CHOP-branch of unfolded protein response (UPR) without influencing the function of other UPR branches, like the ATF4-eIF2α-XBP1 signaling pathway. As a result of impaired ATF6 activation, dermal fibroblasts and adult thyrocytes from ERp29−/− mice display significantly lower apoptosis sensitivities when treated with tunicamycin and hydrogen peroxide. However, in contrast to previous reports, we could demonstrate that ERp29 deficiency does not alter thyroglobulin expression levels. Therefore, our study suggests that ERp29 acts as an escort factor for ATF6 and promotes its transport from ER to Golgi apparatus under ER stress conditions.

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Abbreviations

ERp29:

Endoplasmic reticulum protein 29

PDI:

Protein disulfide isomerase

UPR:

Unfolded protein response

ER:

Endoplasmic reticulum

ERAD:

ER associated degradation

ROS:

Reactive oxygen species

SD:

Standard deviation

Tg:

Thyroglobulin

Tu:

Tunicamycin

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Acknowledgments

We are grateful to all of the members of Max Planck Research Unit for Enzymology of Protein Folding (Halle/Saale, Germany) for helpful discussion, and in part for technical assistance. The present work was supported by grants from the Exzellenznetzwerk Biowissenschaften (Sachsen-Anhalt).

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  1. Max Planck Research Unit for Enzymology of Protein Folding, Weinbergweg 22, 06120, Halle/Saale, Germany

    Irina Hirsch, Matthias Weiwad, Erik Prell & David Michael Ferrari

  2. Institut 20, 06193, Wettin-Löbejün, Germany

    Irina Hirsch

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  1. Irina Hirsch
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Correspondence to Irina Hirsch.

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Hirsch, I., Weiwad, M., Prell, E. et al. ERp29 deficiency affects sensitivity to apoptosis via impairment of the ATF6–CHOP pathway of stress response. Apoptosis 19, 801–815 (2014). https://doi.org/10.1007/s10495-013-0961-0

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