[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-445168-105":3,"detail-sidebar-cat-0-en-105":80,"doc-detail-445168-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":73,"head_meta":75,"extra_data":77,"updated_unix":79},105,"en","deacetylation-of-sod3-by-sirtuins-restores-furin-cleavage","Deacetylation of SOD3 by sirtuins restores furin cleavage","","Accumulation of superoxide radicals disrupts redox signaling and drives oxidative damage. Extracellular superoxide dismutase 3 (SOD3) is the key extracellular superoxide scavenger, with its localization governed by a C-terminal heparin-binding domain (HBD). Furin can remove this HBD through intracellular proteolytic processing, and cleavage is modulated by post-translational cysteine redox status. Lysine acetylation regulates other SOD family members, but its role in SOD3 was unknown. Here, immunoblotting and mass spectrometry quantify global and site-specific acetylation, revealing a PRM MS strategy for the HBD. Acetylation blocks furin cleavage without affecting SOD3 activity, while NAD+-dependent sirtuins deacetylate SOD3 to restore cleavage.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/deacetylation-of-sod3-by-sirtuins-restores-furin-cleavage/445168/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/deacetylation-of-sod3-by-sirtuins-restores-furin-cleavage/445168.png","ImageObject",300,407,{"name":42,"@type":43},"ahduag","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-03","2026-09-29",true,{"@type":52,"interactionType":53,"userInteractionCount":26},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58,64,68],{"name":59,"@type":60,"acceptedAnswer":61},"What role does SOD3 play in redox signaling and oxidative stress?","Question",{"text":62,"@type":63},"SOD3 scavenges extracellular superoxide, helping maintain antioxidant status. Its abundance and proper function are important because organs like the lung and kidney are highly susceptible to oxidative damage.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"How does furin cleavage relate to the structure of SOD3?",{"text":67,"@type":63},"SOD3 contains a C-terminal heparin-binding domain (HBD) that can be recognized and cleaved by the proprotein convertase furin, influencing SOD3 processing prior to secretion and determining extracellular distribution.",{"name":69,"@type":60,"acceptedAnswer":70},"What did acetylation and sirtuin-mediated deacetylation change in SOD3?",{"text":71,"@type":63},"Lysine acetylation within the HBD prevents furin cleavage without impacting SOD3 enzymatic activity. NAD+-dependent sirtuins deacetylate SOD3 and restore furin cleavage, linking redox homeostasis to acetylation-directed regulation of extracellular oxidative stress.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},445168,1791007395,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,109,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":88,"show_sort_weight":89,"slug":90},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":92,"show_sort_weight":93,"slug":94},"Exam",70,"exam",{"id":96,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},5,"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":107,"slug":108},7,40,"healthcare",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},8,"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":96,"slug":129},19,"General","general",{"code":4,"msg":81,"data":131},{"doc_id":78,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":106,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":26,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":127,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":144},3985747870414,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Author Manuscript Author Manuscript Author Manuscript Author Manuscript  \n\n| | HHS Public Access\u003Cbr>Author manuscript\u003Cbr>Redox Biochem Chem. Author manuscript; available in PMC 2026 January 07. |\n| --- | --- |\n\nPublished in final edited form as:  \nRedox Biochem Chem. 2025 December ; 14: . doi:10.1016/j.rbc.2025.100062 .  \nDeacetylation of SOD3 by sirtuins restores furin cleavage  \nEmily C. Mitchema, Peter S. Harrisa, Cole R. Michela, Courtney D. McGinnisa, Shashikant Rayc, Krishna M.G. Mallelaa, James R. Roedea, Steen V. Petersend, Eva S. Nozikb, Kristofer S. Fritza,*  \naSkaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA  \nbCardiovascular Pulmonary Research Laboratories and Pediatric Critical Care, Department of Pediatrics, The University of Colorado Anschutz Medical Center, Aurora, CO, 80045, USAc Department of Biotechnology, Mahatma Gandhi Central University, Motihari, Bihar, India, 845401 d Department of Biomedicine, Aarhus University, Aarhus, Denmark  \nAbstract  \nAccumulation of superoxide radicals leads to disrupted redox signaling and oxidative damage.  \nThe primary extracellular scavenger of superoxide is extracellular superoxide dismutase (SOD3), a crucial enzyme in maintaining antioxidant status and proper immune function. SOD3 distribution to the extracellular matrix is determined by the presence of a C-terminal heparin-binding domain (HBD). This region can be removed through intracellular proteolytic processing by furin. Cleavage ofthe HBD has been shown to be modulated by post-translational cysteine redox status, regulating the secretion of SOD3 . Interestingly, other members of the SOD family, SOD1 and SOD2, are known to be inhibited by lysine acetylation, a metabolically linked post-translational modification (PTM) that can alter protein structure, function, and localization. Yet, no reports describe the effect of acetylation on SOD3. Here, immunoblotting and mass spectrometry (MS) were used to quantify the global and site-specific acetylation of recombinant human SOD3. Interestingly, a predicted and targeted parallel reaction monitoring (PRM) MS-based approach was necessary to identify lysine acetylation within the C-terminal HBD of SOD3. Acetylation was found to prevent furin cleavage with no impact on SOD3 activity. Our results also reveal that SOD3 is robustly deacetylated  \nThis is an open access article under the CC BY license ([http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/)).  \n*Corresponding author. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, 12850 E. Montview Blvd, Mail Stop C238, Aurora, CO 80045, [USA. kristofer.fritz@cuanschutz.edu](USA. kristofer.fritz@cuanschutz.edu) (K.S. Fritz).  \nCRediT authorship contribution statement  \nEmily C. Mitchem: Writing – review & editing, Writing – original draft, Validation, Methodology, Investigation, Formal analysis, Data curation. Peter S. Harris: Writing – review & editing, Methodology, Investigation, Formal analysis. Cole R. Michel: Writing – review & editing, Validation, Methodology, Investigation, Formal analysis, Data curation. Courtney D. McGinnis: Writing – review & editing, Methodology, Investigation. Shashikant Ray: Writing – review & editing, Methodology, Investigation. Krishna M.G. Mallela: Writing – review & editing, Methodology, Investigation. James R. Roede: Writing – review & editing, Resources, Methodology, Conceptualization. Steen V. Petersen: Writing – review & editing, Methodology, Investigation. Eva S. Nozik: Writing – review & editing, Formal analysis, Conceptualization. Kristofer S. Fritz: Writing – review & editing, Writing – original draft, Visualization, Validation, Supervision, Project administration, Methodology, Investigation, Funding acquisition, Formal analysis, Data curation, Conceptualization.  \nDeclaration of competing interest  \nThe authors declare that the","cbCaibt4m9RkxR2k","https://ap.wps.com/l/cbCaibt4m9RkxR2k","pdf",1090005,"English","# Abstract\n# Keywords\n# 1. Introduction","[{\"question\":\"What role does SOD3 play in redox signaling and oxidative stress?\",\"answer\":\"SOD3 scavenges extracellular superoxide, helping maintain antioxidant status. Its abundance and proper function are important because organs like the lung and kidney are highly susceptible to oxidative damage.\"},{\"question\":\"How does furin cleavage relate to the structure of SOD3?\",\"answer\":\"SOD3 contains a C-terminal heparin-binding domain (HBD) that can be recognized and cleaved by the proprotein convertase furin, influencing SOD3 processing prior to secretion and determining extracellular distribution.\"},{\"question\":\"What did acetylation and sirtuin-mediated deacetylation change in SOD3?\",\"answer\":\"Lysine acetylation within the HBD prevents furin cleavage without impacting SOD3 enzymatic activity. NAD+-dependent sirtuins deacetylate SOD3 and restore furin cleavage, linking redox homeostasis to acetylation-directed regulation of extracellular oxidative stress.\"}]","Deacetylation of SOD3 by sirtuins restores furin cleavage | PDF",1790710512,48]