|ZFIN ID: ZDB-PUB-070625-24|
XBP-1, a key regulator of unfolded protein response, activates transcription of IGF1 and Akt phosphorylation in zebrafish embryonic cell line
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.
|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|
|PubMed:||17560942 Full text @ Biochem. Biophys. Res. Commun.|
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.
ABSTRACTThe 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.
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