Endoplasmic reticulum oxidoreductin 1-lbeta (ERO1-Lbeta), a human gene induced in the course of the unfolded protein response.
Oxidative conditions must be generated in the endoplasmic reticulum (ER) to allow disulfide bond formation in secretory proteins. A family of conserved genes, termed ERO for ER oxidoreductins, plays a key role in this process. We have previously described the human gene ERO1-L, which complements several phenotypic traits of the yeast thermo-sensitive mutant ero1-1 (Cabibbo, A., Pagani, M., Fabbri, M., Rocchi, M., Farmery, M. R., Bulleid, N. J., and Sitia, R. (2000) J. Biol. Chem. 275, 4827-4833). Here, we report the cloning and characterization of a novel human member of this family, ERO1-Lbeta. Immunofluorescence, endoglycosidase sensitivity, and in vitro translation/translocation assays reveal that the products of the ERO1-Lbeta gene are primarily localized in the ER of mammalian cells. The ability to allow growth at 37 degrees C and to alleviate the "unfolded protein response" when expressed in ero1-1 cells indicates that ERO1-Lbeta is involved also in generating oxidative conditions in the ER. ERO1-L and ERO1-Lbeta display different tissue distributions. Furthermore, only ERO1-Lbeta transcripts are induced in the course of the unfolded protein response. Our results suggest a complex regulation of ER redox homeostasis in mammalian cells.
Pagani
M
M
Department of Molecular Pathology and Medicine, DIBIT-San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy.
Fabbri
M
M
Benedetti
C
C
Fassio
A
A
Pilati
S
S
Bulleid
N J
NJ
Cabibbo
A
A
Sitia
R
R
D000595:Amino Acid Sequence; D000818:Animals; D002451:Cell Compartmentation; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D015723:Gene Library; D005816:Genetic Complementation Test; D006706:Homeostasis; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000235:genetics*; D050862:Oxidoreductases Acting on Sulfur Group Donors; D017510:Protein Folding; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D008562:Membrane Glycoproteins; C405327:ERO1A protein, human; D010088:Oxidoreductases; D050862:Oxidoreductases Acting on Sulfur Group Donors; C485767:ERO1B protein, human