Oxygen and the copper chaperone CCS regulate posttranslational activation of Cu,Zn superoxide dismutase
- 2 April 2004
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 101 (15), 5518-5523
- https://doi.org/10.1073/pnas.0401175101
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 O(2) (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 O(2) 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.This publication has 32 references indexed in Scilit:
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