title: ERp29 deficiency affects sensitivity to apoptosis via impairment of the ATF6-CHOP pathway of stress response.
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.
authors.affiliation: Max Planck Research Unit for Enzymology of Protein Folding, Weinbergweg 22, 06120, Halle/Saale, Germany, irina-hirsch@gmx.de.
authors.forename: Irina
authors.initials: I
authors.lastname: Hirsch
authors.forename: Matthias
authors.initials: M
authors.lastname: Weiwad
authors.forename: Erik
authors.initials: E
authors.lastname: Prell
authors.forename: David Michael
authors.initials: DM
authors.lastname: Ferrari
mesh_terms: D051702:Activating Transcription Factor 6 / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016877:Oxidants / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D012867:Skin / Q000166:cytology; D013961:Thyroid Gland / Q000166:cytology; D051742:Transcription Factor CHOP / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology; D056811:Unfolded Protein Response / Q000187:drug effects / Q000502:physiology
chemical_list: D051702:Activating Transcription Factor 6; C497112:Atf6 protein, mouse; C497250:Ddit3 protein, mouse; C491737:Erp29 protein, mouse; D006360:Heat-Shock Proteins; D016877:Oxidants; D011500:Protein Synthesis Inhibitors; D014415:Tunicamycin; D051742:Transcription Factor CHOP; D006861:Hydrogen Peroxide