Sumoylation regulates ER stress response by modulating calreticulin gene expression in XBP-1-dependent mode in Caenorhabditis elegans.
Int J Biochem Cell Biol
; 53: 399-408, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-24933177
ABSTRACT
Excessive accumulation of unfolded proteins in the endoplasmic reticulum (ER) lumen causes ER stress, which induces a set of genes, including those encoding ER-resident chaperones, to relieve the detrimental effects and recover homeostasis. Calreticulin is a chaperone that facilitates protein folding in the ER lumen, and its gene expression is induced by ER stress in Caenorhabditis elegans. Sumoylation conjugates small ubiquitin-like modifier (SUMO) proteins with target proteins to regulate a variety of biological processes, such as protein stability, nuclear transport, DNA binding, and gene expression. In this study, we showed that C. elegans X-box-binding protein 1 (Ce-XBP-1), an ER stress response transcription factor, interacts with the SUMO-conjugating enzyme UBC-9 and a SUMOylation target. Our results indicated that abolishing sumoylation enhanced calreticulin expression in an XBP-1-dependent manner, and the resulting increase in calreticulin counteracted ER stress. Furthermore, sumoylation was repressed in C. elegans undergoing ER stress. Finally, RNAi against ubc-9 mainly affected the expression of genes associated with ER functions, such as lipid and organic acid metabolism. Our results suggest that sumoylation plays a regulatory role in ER function by controlling the expression of genes required for ER homeostasis in C. elegans.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte
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Regulação da Expressão Gênica
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Proteínas de Caenorhabditis elegans
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Calreticulina
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Estresse do Retículo Endoplasmático
Limite:
Animals
Idioma:
En
Revista:
Int J Biochem Cell Biol
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2014
Tipo de documento:
Article