PUBLICATION
XBP-1, a key regulator of unfolded protein response, activates transcription of IGF1 and Akt phosphorylation in zebrafish embryonic cell line
- Authors
- Hu, M.C., Gong, H.Y., Lin, G.H., Hu, S.Y., Chen, M.H., Huang, S.J., Liao, C.F., and Wu, J.L.
- ID
- ZDB-PUB-070625-24
- Date
- 2007
- Source
- Biochemical and Biophysical Research Communications 359(3): 778-783 (Journal)
- Registered Authors
- Chen, Mark Hung-Chih, Gong, Hong-Yi, Liao, Ching-Fong, Lin, Gen-Hwa, Wu, Jen-Leih
- Keywords
- XBP-1, Unfolded protein response, ER stress, IGF1, Akt, Anti-apoptosis, Zebrafish
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Cell Line
- Cloning, Molecular
- DNA, Complementary/genetics
- DNA-Binding Proteins/chemistry
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism*
- Endoplasmic Reticulum/metabolism
- Humans
- Insulin-Like Growth Factor I/genetics*
- Molecular Sequence Data
- Oligonucleotide Array Sequence Analysis
- Phosphorylation
- Protein Folding
- Proto-Oncogene Proteins c-akt/metabolism*
- RNA, Messenger/genetics
- Sequence Alignment
- Sequence Homology, Amino Acid
- Signal Transduction
- Time Factors
- Transcription Factors/chemistry
- Transcription Factors/genetics
- Transcription Factors/metabolism*
- Transcription, Genetic/genetics*
- Up-Regulation
- Zebrafish/embryology
- Zebrafish/genetics*
- Zebrafish/metabolism*
- PubMed
- 17560942 Full text @ Biochem. Biophys. Res. Commun.
Citation
Hu, M.C., Gong, H.Y., Lin, G.H., Hu, S.Y., Chen, M.H., Huang, S.J., Liao, C.F., and Wu, J.L. (2007) XBP-1, a key regulator of unfolded protein response, activates transcription of IGF1 and Akt phosphorylation in zebrafish embryonic cell line. Biochemical and Biophysical Research Communications. 359(3):778-783.
Abstract
The unfolded protein response (UPR) is a conserved and adaptive cellular response to increase cell survival during ER stress. XBP-1 spliced form (XBP-1S) generated by IRE1 endoribonuclease is a key transcriptional regulator in UPR to activate genes involved in protein folding and degradation to restore ER function. Although Akt activation was suggested to be a pro-survival pathway activated during ER stress, the signal to trigger Akt is still not clear. In this study, we report IGF1 transcription and Akt phosphorylation are enhanced in XBP-1S stably overexpressed clone of zebrafish embryonic cell line (ZF4). In addition, zebrafish IGF1 intron1 with predicted UPRE (XBP-1S binding sites) and ERSE (ATF6/XBP-1S binding site) linked with basal promoter could be activated by XBP-1S, not by XBP-1 unspliced form (XBP-1U). Furthermore, we demonstrate that expression of endogenous IGF1 is transiently induced as XBP-1 splicing during ER stress in parallel to ER chaperone GRP78/Hspa5 and ER resided E3 ubiquitin ligase Synoviolin in ZF4 cells by quantitative PCR. Our results suggest zebrafish XBP-1S not only activates genes responsible for protein folding, transporting, glycosylation and ER associated degradation but also activates anti-apoptosis signal via IGF1/Akt pathway in unfolded protein response to cope with ER stress.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping