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Signalling from endoplasmic reticulum to nucleus: transcription factor with a basic‐leucine zipper motif is required for the unfolded protein‐response pathway
Author(s) -
Mori Kazutoshi,
Kawahara Tetsushi,
Yoshida Hiderou,
Yanagi Hideki,
Yura Takashi
Publication year - 1996
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1046/j.1365-2443.1996.d01-274.x
Subject(s) - unfolded protein response , biology , endoplasmic reticulum , leucine zipper , transcription factor , microbiology and biotechnology , activating transcription factor , gene , biochemistry
Background : Accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers the transcriptional induction of molecular chaperones and folding enzymes localized in the ER. Thus, eukaryotic cells possess an intracellular signalling pathway from the ER to the nucleus, called the unfolded protein‐response (UPR) pathway. In Saccharomyces cerevisiae, such induction is mediated by the cis ‐acting unfolded protein‐response element (UPRE) which has been thought to be recognized by one or more transcription factor(s). Results : Extensive mutational analysis revealed that UPRE contains a partial palindrome with a spacer of one nucleotide (CAGCGTG) that is essential for its function. We then cloned the ERN4 (presumably identical with HAC1 ) gene using yeast one‐hybrid screening, in which the GAL4‐ERN4 fusion gene constitutively activates the UPR pathway. The ERN4 gene encodes a basic‐leucine zipper protein (Ern4p) that specifically binds to UPRE in vitro and activates transcription in vivo . Cells lacking Ern4p are unable to induce transcription of any of the five target genes tested and exhibit sensitivity to ER stress and inositol requirement for growth. Conclusion : We concluded that Ern4p represents a major component of the putative transcription factor (UPRF) responsible for the UPR leading to the induction of ER‐localized stress proteins.