Cu,Zn Superoxide Dismutase Maturation and Activity Are Regulated by COMMD1 |
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| Authors: | Willianne I. M. Vonk Cisca Wijmenga Ruud Berger Bart van de Sluis Leo W. J. Klomp |
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| Affiliation: | From the ‡Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, and Netherlands Metabolomics Center, 3584 EA Utrecht.;the §Complex Genetics Section, University Medical Center Utrecht, 3584 EA Utrecht, and ;the ¶Department of Genetics and ;‖Department of Pathology and Laboratory Medicine, University Medical Center Groningen, 9713 AV Groningen, The Netherlands |
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| Abstract: | The maturation and activation of the anti-oxidant Cu,Zn superoxide dismutase (SOD1) are highly regulated processes that require several post-translational modifications. The maturation of SOD1 is initiated by incorporation of zinc and copper ions followed by disulfide oxidation leading to the formation of enzymatically active homodimers. Our present data indicate that homodimer formation is a regulated final step in SOD1 maturation and implicate the recently characterized copper homeostasis protein COMMD1 in this process. COMMD1 interacts with SOD1, and this interaction requires CCS-mediated copper incorporation into SOD1. COMMD1 does not regulate disulfide oxidation of SOD1 but reduces the level of SOD1 homodimers. RNAi-mediated knockdown of COMMD1 expression results in a significant induction of SOD1 activity and a consequent decrease in superoxide anion concentrations, whereas overexpression of COMMD1 exerts exactly the opposite effects. Here, we identify COMMD1 as a novel protein regulating SOD1 activation and associate COMMD1 function with the production of free radicals. |
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| Keywords: | Copper Enzyme Inactivation Oxidative Stress Superoxide Dismutase (SOD) Superoxide Ion CCS COMMD1 |
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