Recombinant Human ERO1L alpha Protein, CF

Endoplasmic reticulum oxidoreductase 1-like protein alpha (ERO1L alpha) is an FAD-dependent protein disulfide oxidase. Disulfide bond formation in mammalian endoplasmic reticulum relies on the combined activity of ERO1L and protein disulfide isomerase (PDI), the enzyme responsible for catalyzing protein disulfide formation. During formation of disulfide bonds, ERO1L concurrently produces hydrogen peroxide making it a source of reactive oxygen species production (1, 2). There are two mammalian homologues of ERO1 that share 65% sequence identity (3); ERO1L alpha is more widely expressed while ERO1L beta is present in select tissues (4). Both homologues contain two essential conserved cysteine triads. The N-terminal triad is involved in interaction with PDI whereas the C-terminal triad forms an active site near FAD (4). Both homologues are regulated by the formation of disulfide bonds within the active site cysteines but whereas ERO1L beta is loosely regulated (5), enzyme activity of ERO1L alpha is tightly controlled (6-8). ERO1L alpha has been shown to be critical in hepatic stellate cell proliferation making it a potential target for managing liver fibrosis (9). ERO1L alpha knockdown inhibits cell proliferation, migration, invasion and chemoresistance (10) while overexpression promotes tumor growth and angiogenesis (11). ERO1L alpha is overexpressed in various types of tumors including breast, gastric, and colon cancer where its up-regulation correlates to a poor prognosis (10-13). ERO1L alpha has been proposed to be a clinically promising therapeutic target for ERO1L expressed cancers (10-12).