The Antioxidant Enzyme Methionine Sulfoxide Reductase A (MsrA) Interacts with Jab1/CSN5 and Regulates Its Function
Methionine sulfoxide (MetO) is an oxidative posttranslational modification that primarily occurs under oxidative stress conditions, leading to alteration of protein structure and function. This modification is regulated by MetO reduction through the evolutionarily conserved methionine sulfoxide redu...
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| Format: | Article |
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MDPI AG
2020-05-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/5/452 |
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| author | Beichen Jiang Zachary Adams Shannon Moonah Honglian Shi Julie Maupin-Furlow Jackob Moskovitz |
| author_facet | Beichen Jiang Zachary Adams Shannon Moonah Honglian Shi Julie Maupin-Furlow Jackob Moskovitz |
| author_sort | Beichen Jiang |
| collection | DOAJ |
| description | Methionine sulfoxide (MetO) is an oxidative posttranslational modification that primarily occurs under oxidative stress conditions, leading to alteration of protein structure and function. This modification is regulated by MetO reduction through the evolutionarily conserved methionine sulfoxide reductase (Msr) system. The Msr type A enzyme (MsrA) plays an important role as a cellular antioxidant and promotes cell survival. The ubiquitin- (Ub) like neddylation pathway, which is controlled by the c-Jun activation domain-binding protein-1 (Jab1), also affects cell survival. Jab1 negatively regulates expression of the cell cycle inhibitor cyclin-dependent kinase inhibitor 1B (P27) through binding and targeting P27 for ubiquitination and degradation. Here we report the finding that MsrA interacts with Jab1 and enhances Jab1′s deneddylase activity (removal of Nedd8). In turn, an increase is observed in the level of deneddylated Cullin-1 (Cul-1, a component of E3 Ub ligase complexes). Furthermore, the action of MsrA increases the binding affinity of Jab1 to P27, while MsrA ablation causes a dramatic increase in P27 expression. Thus, an interaction between MsrA and Jab1 is proposed to have a positive effect on the function of Jab1 and to serve as a means to regulate cellular resistance to oxidative stress and to enhance cell survival. |
| first_indexed | 2024-03-10T19:38:02Z |
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| id | doaj.art-c8876085d47947c8be0f41f433494057 |
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| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T19:38:02Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-c8876085d47947c8be0f41f4334940572023-11-20T01:33:23ZengMDPI AGAntioxidants2076-39212020-05-019545210.3390/antiox9050452The Antioxidant Enzyme Methionine Sulfoxide Reductase A (MsrA) Interacts with Jab1/CSN5 and Regulates Its FunctionBeichen Jiang0Zachary Adams1Shannon Moonah2Honglian Shi3Julie Maupin-Furlow4Jackob Moskovitz5Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS 66045, USADepartment of Microbiology and Cell Science, College of Agricultural and Life Sciences, University of Florida, Gainesville, FL 32611, USADivision of Infectious Diseases, University of Virginia, 345 Crispell Drive, MR-6, Room 2715, Charlottesville, VA 22908, USADepartment of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS 66045, USADepartment of Microbiology and Cell Science, College of Agricultural and Life Sciences, University of Florida, Gainesville, FL 32611, USADepartment of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS 66045, USAMethionine sulfoxide (MetO) is an oxidative posttranslational modification that primarily occurs under oxidative stress conditions, leading to alteration of protein structure and function. This modification is regulated by MetO reduction through the evolutionarily conserved methionine sulfoxide reductase (Msr) system. The Msr type A enzyme (MsrA) plays an important role as a cellular antioxidant and promotes cell survival. The ubiquitin- (Ub) like neddylation pathway, which is controlled by the c-Jun activation domain-binding protein-1 (Jab1), also affects cell survival. Jab1 negatively regulates expression of the cell cycle inhibitor cyclin-dependent kinase inhibitor 1B (P27) through binding and targeting P27 for ubiquitination and degradation. Here we report the finding that MsrA interacts with Jab1 and enhances Jab1′s deneddylase activity (removal of Nedd8). In turn, an increase is observed in the level of deneddylated Cullin-1 (Cul-1, a component of E3 Ub ligase complexes). Furthermore, the action of MsrA increases the binding affinity of Jab1 to P27, while MsrA ablation causes a dramatic increase in P27 expression. Thus, an interaction between MsrA and Jab1 is proposed to have a positive effect on the function of Jab1 and to serve as a means to regulate cellular resistance to oxidative stress and to enhance cell survival.https://www.mdpi.com/2076-3921/9/5/452methionine oxidationposttranslational modificationneddylationubiquitinbrainoxidative stress |
| spellingShingle | Beichen Jiang Zachary Adams Shannon Moonah Honglian Shi Julie Maupin-Furlow Jackob Moskovitz The Antioxidant Enzyme Methionine Sulfoxide Reductase A (MsrA) Interacts with Jab1/CSN5 and Regulates Its Function Antioxidants methionine oxidation posttranslational modification neddylation ubiquitin brain oxidative stress |
| title | The Antioxidant Enzyme Methionine Sulfoxide Reductase A (MsrA) Interacts with Jab1/CSN5 and Regulates Its Function |
| title_full | The Antioxidant Enzyme Methionine Sulfoxide Reductase A (MsrA) Interacts with Jab1/CSN5 and Regulates Its Function |
| title_fullStr | The Antioxidant Enzyme Methionine Sulfoxide Reductase A (MsrA) Interacts with Jab1/CSN5 and Regulates Its Function |
| title_full_unstemmed | The Antioxidant Enzyme Methionine Sulfoxide Reductase A (MsrA) Interacts with Jab1/CSN5 and Regulates Its Function |
| title_short | The Antioxidant Enzyme Methionine Sulfoxide Reductase A (MsrA) Interacts with Jab1/CSN5 and Regulates Its Function |
| title_sort | antioxidant enzyme methionine sulfoxide reductase a msra interacts with jab1 csn5 and regulates its function |
| topic | methionine oxidation posttranslational modification neddylation ubiquitin brain oxidative stress |
| url | https://www.mdpi.com/2076-3921/9/5/452 |
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