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Proteolytic Degradation of Tyrosine Nitrated Proteins
Journal article   Peer reviewed

Proteolytic Degradation of Tyrosine Nitrated Proteins

José M. Souza, Irene Choi, Qiping Chen, Marie Weisse, Evgueni Daikhin, Marc Yudkoff, Martin Obin, Jahan Ara, Joel Horwitz and Harry Ischiropoulos
Archives of biochemistry and biophysics, v 380(2), pp 360-366
15 Aug 2000
PMID: 10933892

Abstract

3-nitrotyrosine chymotrypsin proteasome superoxide dismutase tyrosine hydroxylase
Tyrosine nitration is a covalent posttranslational protein modification that has been detected under several pathological conditions. This study reports that nitrated proteins are degraded by chymotrypsin and that protein nitration enhances susceptibility to degradation by the proteasome. Chymotrypsin cleaved the peptide bond between nitrated-tyrosine 108 and serine 109 in bovine Cu,Zn superoxide dismutase. However, the rate of chymotryptic cleavage of nitrated peptides was considerably slower than control. In contrast, nitrated bovine Cu,Zn superoxide dismutase was degraded at a rate 1.8-fold faster than that of control by a gradient-purified 20S/26S proteasome fraction from bovine retina. Exposure of PC12 cells to a nitrating agent resulted in the nitration of tyrosine hydroxylase and a 58 ± 12.5% decline in the steady-state levels of the protein 4 h after nitration. The steady-state levels of tyrosine hydroxylase were restored by selective inhibition of the proteasome activity with lactacystin. These data indicate that nitration of tyrosine residue(s) in proteins is sufficient to induce an accelerated degradation of the modified proteins by the proteasome and that the proteasome may be critical for the removal of nitrated proteins in vivo.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Biophysics
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