Endoplasmic reticulum oxidoreductin 1-L beta (ERO1-L beta), 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 conserve d genes, termed ERO for ER oxidoreductins, plays a key role in this process . We have previously described the human gene ERO1-L, which complements sev eral phenotypic traits of the yeast thermo-sensitive mutant erol-1 (Cabibbo , A., Pagani, M., Fabbri, M., Rocchi, M., Farmery, M. R., Bulleid, N. J., a nd Sitia, R. (2000) J. Biol. Chem. 275, 4827-4833). Here, we report the clo ning and characterization of a novel human member of this family, ERO1-L be ta. Immunofluorescence, endoglycosidase sensitivity, and in vitro translati on/translocation assays reveal that the products of the ERO1-L beta gene ar e primarily localized in the ER of mammalian cells. The ability to allow gr owth at 37 degrees C and to alleviate the "unfolded protein response" when expressed in erol-1 cells indicates that EBO1-L beta is involved also in ge nerating oxidative conditions in the ER, ERO1-L and ERO1-L beta display dif ferent tissue distributions. Furthermore, only ERO1-L beta transcripts are induced in the course of the unfolded protein response. Our results suggest a complex regulation of ER redox homeostasis in mammalian cells.