Search tips
Search criteria 


Logo of mbcLink to Publisher's site
Mol Biol Cell. 1997 September; 8(9): 1805–1814.
PMCID: PMC305738

The unfolded protein response coordinates the production of endoplasmic reticulum protein and endoplasmic reticulum membrane.


The endoplasmic reticulum (ER) is a multifunctional organelle responsible for production of both lumenal and membrane components of secretory pathway compartments. Secretory proteins are folded, processed, and sorted in the ER lumen and lipid synthesis occurs on the ER membrane itself. In the yeast Saccharomyces cerevisiae, synthesis of ER components is highly regulated: the ER-resident proteins by the unfolded protein response and membrane lipid synthesis by the inositol response. We demonstrate that these two responses are intimately linked, forming different branches of the same pathway. Furthermore, we present evidence indicating that this coordinate regulation plays a role in ER biogenesis.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bailis AM, Poole MA, Carman GM, Henry SA. The membrane-associated enzyme phosphatidylserine synthase is regulated at the level of mRNA abundance. Mol Cell Biol. 1987 Jan;7(1):167–176. [PMC free article] [PubMed]
  • Basson ME, Thorsness M, Finer-Moore J, Stroud RM, Rine J. Structural and functional conservation between yeast and human 3-hydroxy-3-methylglutaryl coenzyme A reductases, the rate-limiting enzyme of sterol biosynthesis. Mol Cell Biol. 1988 Sep;8(9):3797–3808. [PMC free article] [PubMed]
  • Carman GM, Henry SA. Phospholipid biosynthesis in yeast. Annu Rev Biochem. 1989;58:635–669. [PubMed]
  • Cox JS, Shamu CE, Walter P. Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase. Cell. 1993 Jun 18;73(6):1197–1206. [PubMed]
  • Cox JS, Walter P. A novel mechanism for regulating activity of a transcription factor that controls the unfolded protein response. Cell. 1996 Nov 1;87(3):391–404. [PubMed]
  • Culbertson MR, Henry SA. Inositol-requiring mutants of Saccharomyces cerevisiae. Genetics. 1975 May;80(1):23–40. [PubMed]
  • Elble R. A simple and efficient procedure for transformation of yeasts. Biotechniques. 1992 Jul;13(1):18–20. [PubMed]
  • Favaloro J, Treisman R, Kamen R. Transcription maps of polyoma virus-specific RNA: analysis by two-dimensional nuclease S1 gel mapping. Methods Enzymol. 1980;65(1):718–749. [PubMed]
  • Gething MJ, Sambrook J. Protein folding in the cell. Nature. 1992 Jan 2;355(6355):33–45. [PubMed]
  • Greenberg ML, Lopes JM. Genetic regulation of phospholipid biosynthesis in Saccharomyces cerevisiae. Microbiol Rev. 1996 Mar;60(1):1–20. [PMC free article] [PubMed]
  • Hirsch JP, Henry SA. Expression of the Saccharomyces cerevisiae inositol-1-phosphate synthase (INO1) gene is regulated by factors that affect phospholipid synthesis. Mol Cell Biol. 1986 Oct;6(10):3320–3328. [PMC free article] [PubMed]
  • Hood DA, Balaban A, Connor MK, Craig EE, Nishio ML, Rezvani M, Takahashi M. Mitochondrial biogenesis in striated muscle. Can J Appl Physiol. 1994 Mar;19(1):12–48. [PubMed]
  • Ito H, Fukuda Y, Murata K, Kimura A. Transformation of intact yeast cells treated with alkali cations. J Bacteriol. 1983 Jan;153(1):163–168. [PMC free article] [PubMed]
  • Kodaki T, Hosaka K, Nikawa J, Yamashita S. Identification of the upstream activation sequences responsible for the expression and regulation of the PEM1 and PEM2 genes encoding the enzymes of the phosphatidylethanolamine methylation pathway in Saccharomyces cerevisiae. J Biochem. 1991 Feb;109(2):276–287. [PubMed]
  • Kozutsumi Y, Segal M, Normington K, Gething MJ, Sambrook J. The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins. Nature. 1988 Mar 31;332(6163):462–464. [PubMed]
  • Mori K, Ma W, Gething MJ, Sambrook J. A transmembrane protein with a cdc2+/CDC28-related kinase activity is required for signaling from the ER to the nucleus. Cell. 1993 Aug 27;74(4):743–756. [PubMed]
  • Mori K, Kawahara T, Yoshida H, Yanagi H, Yura T. Signalling from endoplasmic reticulum to nucleus: transcription factor with a basic-leucine zipper motif is required for the unfolded protein-response pathway. Genes Cells. 1996 Sep;1(9):803–817. [PubMed]
  • Nikawa J, Akiyoshi M, Hirata S, Fukuda T. Saccharomyces cerevisiae IRE2/HAC1 is involved in IRE1-mediated KAR2 expression. Nucleic Acids Res. 1996 Nov 1;24(21):4222–4226. [PMC free article] [PubMed]
  • Nikawa J, Yamashita S. IRE1 encodes a putative protein kinase containing a membrane-spanning domain and is required for inositol phototrophy in Saccharomyces cerevisiae. Mol Microbiol. 1992 Jun;6(11):1441–1446. [PubMed]
  • Nunnari J, Walter P. Regulation of organelle biogenesis. Cell. 1996 Feb 9;84(3):389–394. [PubMed]
  • Shamu CE, Cox JS, Walter P. The unfolded-protein-response pathway in yeast. Trends Cell Biol. 1994 Feb;4(2):56–60. [PubMed]
  • Shamu CE, Walter P. Oligomerization and phosphorylation of the Ire1p kinase during intracellular signaling from the endoplasmic reticulum to the nucleus. EMBO J. 1996 Jun 17;15(12):3028–3039. [PubMed]
  • Sherman F. Getting started with yeast. Methods Enzymol. 1991;194:3–21. [PubMed]
  • Sidrauski C, Cox JS, Walter P. tRNA ligase is required for regulated mRNA splicing in the unfolded protein response. Cell. 1996 Nov 1;87(3):405–413. [PubMed]
  • Sweet DJ. A kinase that responds to stress. Curr Biol. 1993 Sep 1;3(9):622–624. [PubMed]
  • White MJ, Hirsch JP, Henry SA. The OPI1 gene of Saccharomyces cerevisiae, a negative regulator of phospholipid biosynthesis, encodes a protein containing polyglutamine tracts and a leucine zipper. J Biol Chem. 1991 Jan 15;266(2):863–872. [PubMed]
  • Wiest DL, Burkhardt JK, Hester S, Hortsch M, Meyer DI, Argon Y. Membrane biogenesis during B cell differentiation: most endoplasmic reticulum proteins are expressed coordinately. J Cell Biol. 1990 May;110(5):1501–1511. [PMC free article] [PubMed]
  • Wright R, Basson M, D'Ari L, Rine J. Increased amounts of HMG-CoA reductase induce "karmellae": a proliferation of stacked membrane pairs surrounding the yeast nucleus. J Cell Biol. 1988 Jul;107(1):101–114. [PMC free article] [PubMed]

Articles from Molecular Biology of the Cell are provided here courtesy of American Society for Cell Biology