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UDP-glucuronosyltransferase1A1 directly binds to albumin. | LitMetric
UDP-glucuronosyltransferase1A1 (UGT1A1) catalyses glucuronidation of bilirubin (the final break down product of heme which is produced mainly in the spleen and liver) and is located on the lumen of the endoplasmic reticulum (ER). To identify partner UGTs that form hetero-oligomers with UGT1A1, or other proteins that bind directly to UGT1A1, yeast two-hybrid screening was performed using UGT1A1 as bait. From these studies, cDNA clones specific for human serum albumin (HSA) were unexpectedly isolated. The direct interaction between UGT1A1 and albumin was confirmed in vitro by a pull-down assay. FITC-albumin uptake into HepG2 and Huh7 cells was observed only when bilirubin are present in the culture medium. Furthermore, the endocytosis inhibitor phenylarsine oxide (PAO) prevented albumin uptake into the cells, suggesting that the albumin/bilirubin complex is internalized through receptor-mediated endocytosis. From these studies, it would appear that production of large amounts of toxic bilirubin might use different uptake pathways for entry into hepatocytes.
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