Signalling from endoplasmic reticulum to nucleus: transcription factor with a basic-leucine zipper motif is required for the unfolded protein-response pathway.
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.


CONCLUSIONS
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.
Mori
K
K
HSP Research Institute, Kyoto Research Park, Shimogyo-ku, Japan.
Kawahara
T
T
Yoshida
H
H
Yanagi
H
H
Yura
T
T
D000595:Amino Acid Sequence; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D002467:Cell Nucleus / Q000502:physiology*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004721:Endoplasmic Reticulum / Q000502:physiology*; D005656:Fungal Proteins / Q000502:physiology*; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D009154:Mutation; D017510:Protein Folding; D011506:Proteins / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology*; D001616:beta-Galactosidase / Q000235:genetics
D050976:Basic-Leucine Zipper Transcription Factors; D005656:Fungal Proteins; C091341:HAC1 protein, S cerevisiae; D011506:Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D001616:beta-Galactosidase