Work

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

Year: 2005

Type: article

Abstract: 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.

Source: American Journal of Hematology

DOI: 10.1002/ajh.20351

Authors: Tsui‐Ling Chang, David G. Kakhniashvili, Steven R. Goodman

Institutions: The University of Texas at Dallas, The University of Texas Southwestern Medical Center

Language: English

Topic: Hemoglobinopathies and Related Disorders

Subfield: Genetics (clinical)

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Institutes of Health, National Heart, Lung, and Blood Institute