Journal
APOPTOSIS
Volume 19, Issue 5, Pages 801-815Publisher
SPRINGER
DOI: 10.1007/s10495-013-0961-0
Keywords
Endoplasmic reticulum protein 29 (ERp29); Unfolded protein response (UPR); ATF6; Thyroglobulin Apoptosis
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Funding
- Exzellenznetzwerk Biowissenschaften (Sachsen-Anhalt)
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Endoplasmic reticulum protein 29 (ERp29) belongs to the redox-inactive PDI-D beta-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-eIF2 alpha-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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