Oxygen and the copper chaperone CCS regulate posttranslational activation of Cu,Zn superoxide dismutase

Nina M. Brown, Andrew S. Torres, Peter E. Doan, Thomas V. O'Halloran*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Oxidative stress leads to the up-regulation of many antioxidant enzymes including Cu,Zn superoxide dismutase (SOD1) via transcriptional mechanisms; however, few examples of posttranslational regulation are known. The copper chaperone for SOD1 (CCS) is involved in physiological SOD1 activation, and its primary function is thought to be delivery of copper to the enzyme. Data presented here are consistent with a previously uncharacterized function for CCS in the SOD1 pathway, namely mediating enzyme activation in response to increases in oxygen tension. Activity assays with pure proteins and cell extracts reveal that O2 (or superoxide) is required for activation of SOD1 by CCS. Dose-response studies with a translational blocking agent demonstrate that the cellular oxidative response to O2 is multitiered: existing apo-pools of SOD1 are activated by CCS in the early response, followed by increasing expression of SOD1 protein with persistent oxidative stress. This CCS function provides oxidant-responsive posttranslational regulation of SOD1 activity and may be relevant to a wide array of physiological stresses that involve a sudden elevation of oxygen availability.

Original languageEnglish (US)
Pages (from-to)5518-5523
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number15
DOIs
StatePublished - Apr 13 2004

ASJC Scopus subject areas

  • General

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