|
KMID : 0381120080300050477
|
|
Genes and Genomics
2008 Volume.30 No. 5 p.477 ~ p.485
|
|
|
Visualization of Protein-Protein Interactions between bZIP Transcription Factors in the Unfolded Protein Response Using BiFC Analysis
|
|
Cho Wang-Sik
Lee Sang-Gyu
Jeong Mini
Cho Jae-Wook
Lee Kyung-Ho
|
|
|
Abstract
|
|
|
|
The unfolded protein response (UPR) is a transcriptional and translational intracellular signaling pathway activated by the accumulation of unfolded proteins in the lumen of the endoplasmic reticulum (ER). Upon the accumulation of unfolded proteins in the ER, sensor proteins located in the ER membrane are activated and initiate an adaptive response via the induction or activation of the transcription factors XBP1, ATF6, and ATF4. In this study, we used a bimolecular fluorescence complementation (BiFC) assay to visualize the interactions among the bZIP transcription factors that function in the UPR. Dimers were formed by spliced forms of XBP1 in the nucleus; however, no dimerization was observed when ZIP domain-deleted XBP1 was used. Using UPRE as a reporter gene, high levels of transcriptional activity were observed with wild-type XBP1; however, activity was totally abolished by the deletion of the first half of the ZIP domain (residues 98 112). Residues 1-36, 167-371, and 256-371 from the XBP1 N- and C-termini were not required for either dimerization or nuclear localization. Interestingly, the deletion of residues 167-371 enhanced the fluorescence intensity. XBP1 also formed heterodimers with ATF6 and ATF4, and the ZIP domain was essential for complex formation. These results suggest that dimer formation through the ZIP domain is essential for proper functioning of the bZIP transcription factors that act in the UPR and that UPR signals originating from different sensor proteins cooperate to activate different sets of target genes via bZIP transcription factors.
|
|
|
KEYWORD
|
|
|
BiFC, XBP1, ER stress, living cells, unfolded protein response (UPR)
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
 
|
|