Spectrin's E2/E3 ubiquitin conjugating/ligating activity is diminished in sickle cells.
Am J Hematol
; 79(2): 89-96, 2005 Jun.
Article
en En
| MEDLINE
| ID: mdl-15929114
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Sanguíneas
/
Espectrina
/
Enzimas Ubiquitina-Conjugadoras
/
Ubiquitina-Proteína Ligasas
/
Anemia de Células Falciformes
Límite:
Humans
Idioma:
En
Revista:
Am J Hematol
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos