Spectrin's E2/E3 ubiquitin conjugating/ligating activity is diminished in sickle cells.

Erythrocyte spectrin contains E2/E3 ubiquitin conjugating/ligating activity in its alpha subunit. Ankyrin is a target of spectrin's E2/E3 ubiquitin conjugating/ligating activity in vitro and in vivo. We compare the ubiquitination levels of ankyrin mediated by control and sickle cell spectrin using a biotinylated ubiquitin cell-free assay. Sickle cell spectrin has ...
diminished ability to transfer ubiquitin from an intermediate spectrin-ubiquitin thioester adduct (alpha' spectrin) to ankyrin, which may be due to glutathiolation of spectrin's E2 and/or E3 active site cysteines. There is also a diminished ability of the sickle cell ankyrin to serve as target of spectrin's E2/E3 activity, probably due to oxidative damage to ankyrin. A direct correlation exists between the alpha'/alpha spectrin ratio and spectrin's ability to ubiquitinate ankyrin. There is also an inverse correlation between severity of the disease and the alpha'/alpha spectrin ratio in SS erythrocytes. These results suggest that reduced spectrin E2/E3 activity is an important determinant of sickle cell severity.
Mesh Terms:
Anemia, Sickle Cell, Ankyrins, Blood Cells, Erythrocytes, Humans, Ligands, Protein Isoforms, Severity of Illness Index, Spectrin, Ubiquitin, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases
Am. J. Hematol.
Date: Jun. 01, 2005
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