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

Tsui Ling Chang, David G. Kakhniashvili, Steven Goodman

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Erythrocyte spectrin contains E2/E3 ubiquitin conjugating/ligating activity in its α 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 (α′ 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 α′/α spectrin ratio and spectrin's ability to ubiquitinate ankyrin. There is also an inverse correlation between severity of the disease and the α′/α spectrin ratio in SS erythrocytes. These results suggest that reduced spectrin E2/ E3 activity is an important determinant of sickle cell severity.

Original languageEnglish (US)
Pages (from-to)89-96
Number of pages8
JournalAmerican Journal of Hematology
Volume79
Issue number2
DOIs
StatePublished - Jun 1 2005

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Spectrin
Ubiquitin
Ankyrins
Erythrocytes
Ubiquitination
Cysteine
Catalytic Domain

All Science Journal Classification (ASJC) codes

  • Hematology

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Spectrin's E2/E3 ubiquitin conjugating/ligating activity is diminished in sickle cells. / Chang, Tsui Ling; Kakhniashvili, David G.; Goodman, Steven.

In: American Journal of Hematology, Vol. 79, No. 2, 01.06.2005, p. 89-96.

Research output: Contribution to journalArticle

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