title: Sumoylation regulates ER stress response by modulating calreticulin gene expression in XBP-1-dependent mode in Caenorhabditis elegans.
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.
authors.affiliation: College of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju 500-712, Republic of Korea.
authors.forename: Yunki
authors.initials: Y
authors.lastname: Lim
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2S7.
authors.forename: Dukgyu
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Life Science, School of Natural Science, Hanyang University, Seoul 133-791, Republic of Korea; BK21 PLUS Life Science for BDR Team, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Karunambigai
authors.initials: K
authors.lastname: Kalichamy
authors.affiliation: College of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju 500-712, Republic of Korea.
authors.forename: Seong-Eui
authors.initials: SE
authors.lastname: Hong
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2S7.
authors.forename: Marek
authors.initials: M
authors.lastname: Michalak
authors.affiliation: Department of Life Science, School of Natural Science, Hanyang University, Seoul 133-791, Republic of Korea; BK21 PLUS Life Science for BDR Team, Hanyang University, Seoul 133-791, Republic of Korea; The Research Institute for Natural Science, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Joohong
authors.initials: J
authors.lastname: Ahnn
authors.affiliation: College of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju 500-712, Republic of Korea. Electronic address: dhkim@gist.ac.kr.
authors.forename: Do Han
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Life Science, School of Natural Science, Hanyang University, Seoul 133-791, Republic of Korea; BK21 PLUS Life Science for BDR Team, Hanyang University, Seoul 133-791, Republic of Korea; The Research Institute for Natural Science, Hanyang University, Seoul 133-791, Republic of Korea. Electronic address: sunkyungl@hanyang.ac.kr.
authors.forename: Sun-Kyung
authors.initials: SK
authors.lastname: Lee
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis*; D037282:Calreticulin / Q000096:biosynthesis*; D002352:Carrier Proteins / Q000096:biosynthesis*; D004721:Endoplasmic Reticulum / Q000235:genetics; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D017510:Protein Folding; D058207:Sumoylation / Q000235:genetics; D044763:Ubiquitin-Conjugating Enzymes / Q000096:biosynthesis
chemical_list: D029742:Caenorhabditis elegans Proteins; D037282:Calreticulin; D002352:Carrier Proteins; C548541:XBP-1 protein, C elegans; D044763:Ubiquitin-Conjugating Enzymes
keywords: Calreticulin; ER stress; Sumoylation; UBC-9; XBP-1