Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase

@article{Cox1993TranscriptionalIO,
  title={Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase},
  author={Jeffery S. Cox and Caroline E. Shamu and Peter Walter},
  journal={Cell},
  year={1993},
  volume={73},
  pages={1197-1206}
}
The transcription of genes encoding soluble proteins that reside in the endoplasmic reticulum (ER) is induced when unfolded proteins accumulate in the ER. Thus, an intracellular signal transduction pathway must exist that mediates communication between the ER lumen and the nucleus. We have identified a gene in S. cerevisiae, IRE1, that is required for this pathway: ire1- mutants cannot activate transcription of KAR2 and PDI1, which encode the ER resident proteins BiP and protein disulfide… Expand
IRE1 and efferent signaling from the endoplasmic reticulum.
TLDR
Surprisingly, mammalian IRE1s are able to activate both JUN N-terminal kinases and an alternative ER-stress signaling pathway mediated by the transcription factor ATF6, indicating that the mammalian UPR is more complex than that found in yeast. Expand
The Unfolded Protein Response Pathway in Saccharomyces cerevisiae
TLDR
It is shown that the cytoplasmic domain of Ire1p receptor indeed has intrinsic Ser/Thr kinase activity and contains Ser/ Thr phosphorylation sites as well and is shown to form oligomers in vivo and in vitro. Expand
Molecular characterization of two Arabidopsis Ire1 homologs, endoplasmic reticulum-located transmembrane protein kinases.
TLDR
Functional complementation of the sensor domains of the two proteins in yeast and show that the Ire1-2 protein is capable of autotransphosphorylation are demonstrated in relation to the involvement of these genes in unfolded protein response signaling in plants. Expand
The Transmembrane Kinase Ire1p Is a Site-Specific Endonuclease That Initiates mRNA Splicing in the Unfolded Protein Response
TLDR
It is shown that Ire1p is a bifunctional enzyme: in addition to being a kinase, it is a site-specific endoribonuclease that cleaves HAC1 mRNA specifically at both splice junctions and the addition of purified tRNA ligase completes splicing. Expand
Oligomerization and phosphorylation of the Ire1p kinase during intracellular signaling from the endoplasmic reticulum to the nucleus.
TLDR
Molecular genetic and biochemical studies described here suggest that, as in the case of growth factor receptors of higher eukaryotic cells, Ire1p oligomerizes in response to the accumulation of unfolded proteins in the ER and is phosphorylated in trans by otherIre1p molecules as a result of oligomerization. Expand
Molecular Characterization of Two Arabidopsis Ire 1 Homologs , Endoplasmic Reticulum-Located Transmembrane Protein Kinases 1
A major response of eukaryotic cells to the presence of unfolded proteins in the lumen of the endoplasmic reticulum (ER) is to activate genes that encode ER-located molecular chaperones, such as theExpand
Regulation of Sumo mRNA during Endoplasmic Reticulum Stress
TLDR
It is shown that Smt3, a homolog of small ubiquitin-like modifier (sumo), is a non-canonical RIDD target in Drosophila S2 cells and unlike other RIDd targets, the sumo transcript does not stably associate with the ER membrane, but instead relies on an Xbp1-like stem loop and a second UPR mediator, Perk, for its degradation during stress. Expand
Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress
TLDR
Another pathway in which the ER transmembrane kinase/ribonuclease IRE1β induces translational repression through 28S ribosomal RNA cleavage in response to ER stress is reported. Expand
Protein Serine/Threonine Phosphatase Ptc2p Negatively Regulates the Unfolded-Protein Response by Dephosphorylating Ire1p Kinase
TLDR
It is demonstrated that Ptc2p downregulates the UPR by dephosphorylating Ire1p and reveal a novel mechanism of regulation in theUPR pathway upstream of the HAC1 mRNA splicing event. Expand
Identification of the cis-Acting Endoplasmic Reticulum Stress Response Element Responsible for Transcriptional Induction of Mammalian Glucose-regulated Proteins
TLDR
The results suggest that, as in yeast, bZIP proteins are involved in mammalian UPR, acting through newly defined ERSE,acting through newlydefined ERSE. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 71 REFERENCES
The promoter region of the yeast KAR2 (BiP) gene contains a regulatory domain that responds to the presence of unfolded proteins in the endoplasmic reticulum.
TLDR
Evidence is provided suggesting that yeast cells monitor the concentration of free BiP in the ER and adjust the level of transcription of the KAR2 gene accordingly; this effect is mediated via the UPR element in the Kar2 promoter. Expand
ERD1, a yeast gene required for the retention of luminal endoplasmic reticulum proteins, affects glycoprotein processing in the Golgi apparatus.
TLDR
It is suggested that sorting of luminal ER proteins normally occurs in the Golgi, and that the function of ERD1 is required for the correct interaction of an HDEL receptor with its ligands, a conclusion supported by analysis of ERd1‐SUC2 fusion proteins. Expand
The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins
TLDR
Testing the hypothesis that the presence of malfolded proteins may be the primary signal for induction of GRPs by expressing wild-type and mutant forms of influenza virus haemagglutinin in simian cells shows that malfoldingper se, rather than abnormal glycosylation1, is the proximal inducer of this family of stress proteins. Expand
The yeast EUG1 gene encodes an endoplasmic reticulum protein that is functionally related to protein disulfide isomerase.
TLDR
The results indicate that PDI1 and EUG1 encode functionally related proteins that are likely to be involved in interacting with nascent polypeptides in the yeast endoplasmic reticulum. Expand
A 22 bp cis‐acting element is necessary and sufficient for the induction of the yeast KAR2 (BiP) gene by unfolded proteins.
TLDR
These experiments show that yeast cells can activate a transcription factor that stimulates expression of a nuclear gene in response to the accumulation of unfolded proteins in another cellular compartment. Expand
S. cerevisiae encodes an essential protein homologous in sequence and function to mammalian BiP
TLDR
It is suggested that deficiencies in BiP may cause generalized failure of protein folding in the ER, leading to pleiotropic effects on cellular metabolism. Expand
IRE1 encodes a putative protein kinase containing a membrane‐spanning domain and is required for inositol phototrophy in Saccharomyces cerevisiae
TLDR
The predicted amino acid sequence indicated that IRE1 encodes a protein of 126983 Da with two highly hydrophobic regions, probably a signal sequence and a membrane‐spanning region, which is very likely a protein kinase required for myo‐inositol synthesis. Expand
Overexpression of GRP78 mitigates stress induction of glucose regulated proteins and blocks secretion of selective proteins in Chinese hamster ovary cells.
TLDR
The results indicate that one function of GRP78 is selective protein retention in the ER, which may increase stable association and decrease the secretion efficiency of proteins which normally transiently associate withGRP78. Expand
Competitive inhibition of a set of endoplasmic reticulum protein genes (GRP78, GRP94, and ERp72) retards cell growth and lowers viability after ionophore treatment.
  • X. Li, A. Lee
  • Biology, Medicine
  • Molecular and cellular biology
  • 1991
TLDR
Results provide new evidence that ERp72 shares common trans-acting regulatory factors with the GRP genes and that a reduction of this set of ER proteins correlates with lower viability after ionophore treatment. Expand
The TMK1 gene from Arabidopsis codes for a protein with structural and biochemical characteristics of a receptor protein kinase.
TLDR
Genomic and cDNA clones that code for a protein with structural and biochemical properties similar to the receptor protein kinases from animals were obtained from Arabidopsis, and the gene coding for this receptor-like transmembrane kinase was designated TMK1. Expand
...
1
2
3
4
5
...