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Science 329 (5998): 1534-1537

Copyright © 2010 by the American Association for the Advancement of Science

Differential Arginylation of Actin Isoforms Is Regulated by Coding Sequence–Dependent Degradation

Fangliang Zhang,1 Sougata Saha,1 Svetlana A. Shabalina,2 Anna Kashina1,*

Abstract: The mammalian cytoskeletal proteins β- and {gamma}-actin are highly homologous, but only β-actin is amino-terminally arginylated in vivo, which regulates its function. We examined the metabolic fate of exogenously expressed arginylated and nonarginylated actin isoforms. Arginylated {gamma}-actin, unlike β-, was highly unstable and was selectively ubiquitinated and degraded in vivo. This instability was regulated by the differences in the nucleotide coding sequence between the two actin isoforms, which conferred different translation rates. {gamma}-actin was translated more slowly than β-actin, and this slower processing resulted in the exposure of a normally hidden lysine residue for ubiquitination, leading to the preferential degradation of {gamma}-actin upon arginylation. This degradation mechanism, coupled to nucleotide coding sequence, may regulate protein arginylation in vivo.

1 Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
2 National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.

* To whom correspondence should be addressed. E-mail: akashina{at}

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