ER stress response induced by the production of human IL-7 in rice endosperm cells.
Plant Mol Biol
; 81(4-5): 461-75, 2013 Mar.
Article
em En
| MEDLINE
| ID: mdl-23371559
ABSTRACT
Rice seed has been used as a production platform for high value recombinant proteins. When mature human interleukin 7 (hIL-7) was expressed as a secretory protein in rice endosperm by ligating the N terminal glutelin signal peptide and the C terminal KDEL endoplasmic reticulum (ER) retention signal to the hIL-7 cytokine to improve production yield, this protein accumulated at levels visible by Coomassie Brilliant Blue staining. However, the production of this protein led not only to a severe reduction of endogenous seed storage proteins but also to a deterioration in grain quality. The appearance of aberrant grain phenotypes (such as floury and shrunken) was attributed to ER stress induced by the retention of highly aggregated unfolded hIL-7 in the ER lumen, and the expression levels of chaperones such as BiPs and PDIs were enhanced in parallel with the increase in hIL-7 levels. The activation of this ER stress response was shown to be mainly mediated by the OsIRE1-OsbZIP50 signal cascade, based on the appearance of unconventional splicing of OsbZIP50 mRNA and the induction of OsBiP4&5. Interestingly, the ER stress response could be induced by lower concentrations of hIL-7 versus other types of cytokines such as IL-1b, IL-4, IL-10, and IL-18. Furthermore, several ubiquitin 26S proteasome-related genes implicated in ER-associated degradation were upregulated by hIL-7 production. These results suggest that severe detrimental effects on grain properties were caused by proteo-toxicity induced by unfolded hIL-7 aggregates in the ER, resulting in the triggering of ER stress.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oryza
/
Interleucina-7
/
Endosperma
/
Estresse do Retículo Endoplasmático
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Plant Mol Biol
Assunto da revista:
BIOLOGIA MOLECULAR
/
BOTANICA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Japão