Dkk3/REIC, an N-glycosylated Protein, Is a Physiological Endoplasmic Reticulum Stress Inducer in the Mouse Adrenal Gland.
Dkk3 knockout mouse
adrenal gland
endoplasmic reticulum stress
glucose-regulated protein 78
proteome
Journal
Acta medica Okayama
ISSN: 0386-300X
Titre abrégé: Acta Med Okayama
Pays: Japan
ID NLM: 0417611
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
entrez:
25
6
2020
pubmed:
25
6
2020
medline:
2
4
2021
Statut:
ppublish
Résumé
Dickkopf 3 (Dkk3) is a secreted protein belonging to the Dkk family and encoded by the orthologous gene of REIC. Dkk3/REIC is expressed by mouse and human adrenal glands, but the understanding of its roles in this organ is still limited. To determine the functions of Dkk3 in the mouse adrenal gland, we first identified that the mouse Dkk3 protein is N-glycosylated in the adrenal gland as well as in the brain. We performed proteome analysis on adrenal glands from Dkk3-null mice, in which exons 5 and 6 of the Dkk3 gene are deleted. Twodimensional polyacrylamide gel electrophoresis of adrenal proteins from wild-type and Dkk3-null mice revealed 5 protein spots whose intensities were altered between the 2 genotypes. Mass spectrometry analysis of these spots identified binding immunoglobulin protein (BiP), an endoplasmic reticulum (ER) chaperone. To determine whether mouse Dkk3 is involved in the unfolded protein response (UPR), we carried out a reporter assay using ER-stress responsive elements. Forced expression of Dkk3 resulted in the induction of distinct levels of reporter expression, showing the UPR initiated by the ER membrane proteins of activating transcription factor 6 (ATF6) and inositol-requring enzyme 1 (IRE1). Thus, it is possible that Dkk3 is a physiological ER stressor in the mouse adrenal gland.
Substances chimiques
Adaptor Proteins, Signal Transducing
0
DKK3 protein, human
0
Dkk3 protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
199-208Déclaration de conflit d'intérêts
No potential conflict of interest relevant to this article was reported.
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