Positive Regulation of Interleukin-1β Bioactivity by Physiological ROS-Mediated Cysteine S-Glutathionylation.
Identifieur interne : 000328 ( Main/Exploration ); précédent : 000327; suivant : 000329Positive Regulation of Interleukin-1β Bioactivity by Physiological ROS-Mediated Cysteine S-Glutathionylation.
Auteurs : Xue Zhang [États-Unis] ; Peng Liu [République populaire de Chine] ; Christie Zhang [États-Unis] ; Direkrit Chiewchengchol [États-Unis] ; Fan Zhao [République populaire de Chine] ; Hongbo Yu [États-Unis] ; Jingyu Li [États-Unis] ; Hiroto Kambara [États-Unis] ; Kate Y. Luo [États-Unis] ; Arvind Venkataraman [États-Unis] ; Ziling Zhou [États-Unis] ; Weidong Zhou [États-Unis] ; Haiyan Zhu [République populaire de Chine] ; Li Zhao [États-Unis] ; Jiro Sakai [États-Unis] ; Yuanyuan Chen [États-Unis] ; Ye-Shih Ho [États-Unis] ; Besnik Bajrami [États-Unis] ; Bing Xu [États-Unis] ; Leslie E. Silberstein [États-Unis] ; Tao Cheng [République populaire de Chine] ; Yuanfu Xu [République populaire de Chine] ; Yuehai Ke [États-Unis] ; Hongbo R. Luo [États-Unis]Source :
- Cell reports [ 2211-1247 ] ; 2017.
Descripteurs français
- KwdFr :
- Animaux (MeSH), Cellules de la moelle osseuse (métabolisme), Cystéine (métabolisme), Espèces réactives de l'oxygène (métabolisme), Glutarédoxines (métabolisme), Glutathion (métabolisme), Interleukine-1 bêta (composition chimique), Interleukine-1 bêta (métabolisme), Maturation post-traductionnelle des protéines (MeSH), Motifs d'acides aminés (MeSH), Mâle (MeSH), Souris (MeSH), Souris de lignée C57BL (MeSH).
- MESH :
- composition chimique : Interleukine-1 bêta.
- métabolisme : Cellules de la moelle osseuse, Cystéine, Espèces réactives de l'oxygène, Glutarédoxines, Glutathion, Interleukine-1 bêta.
- Animaux, Maturation post-traductionnelle des protéines, Motifs d'acides aminés, Mâle, Souris, Souris de lignée C57BL.
English descriptors
- KwdEn :
- Amino Acid Motifs (MeSH), Animals (MeSH), Bone Marrow Cells (metabolism), Cysteine (metabolism), Glutaredoxins (metabolism), Glutathione (metabolism), Interleukin-1beta (chemistry), Interleukin-1beta (metabolism), Male (MeSH), Mice (MeSH), Mice, Inbred C57BL (MeSH), Protein Processing, Post-Translational (MeSH), Reactive Oxygen Species (metabolism).
- MESH :
- chemical , chemistry : Interleukin-1beta.
- chemical , metabolism : Cysteine, Glutaredoxins, Glutathione, Interleukin-1beta, Reactive Oxygen Species.
- metabolism : Bone Marrow Cells.
- Amino Acid Motifs, Animals, Male, Mice, Mice, Inbred C57BL, Protein Processing, Post-Translational.
Abstract
Reactive oxygen species (ROS)-induced cysteine S-glutathionylation is an important posttranslational modification (PTM) that controls a wide range of intracellular protein activities. However, whether physiological ROS can modulate the function of extracellular components via S-glutathionylation is unknown. Using a screening approach, we identified ROS-mediated cysteine S-glutathionylation on several extracellular cytokines. Glutathionylation of the highly conserved Cys-188 in IL-1β positively regulates its bioactivity by preventing its ROS-induced irreversible oxidation, including sulfinic acid and sulfonic acid formation. We show this mechanism protects IL-1β from deactivation by ROS in an in vivo system of irradiation-induced bone marrow (BM) injury. Glutaredoxin 1 (Grx1), an enzyme that catalyzes deglutathionylation, was present and active in the extracellular space in serum and the BM, physiologically regulating IL-1β glutathionylation and bioactivity. Collectively, we identify cysteine S-glutathionylation as a cytokine regulatory mechanism that could be a therapeutic target in the treatment of various infectious and inflammatory diseases.
DOI: 10.1016/j.celrep.2017.05.070
PubMed: 28683316
PubMed Central: PMC5758045
Affiliations:
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Le document en format XML
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Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 01605, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Hematopathology, Flow Cytometry, Hematology, and Blood Bank Labs, VA Boston Healthcare System, West Roxbury, MA 02132, USA; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 01605</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Li, Jingyu" sort="Li, Jingyu" uniqKey="Li J" first="Jingyu" last="Li">Jingyu Li</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; 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Luo</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Venkataraman, Arvind" sort="Venkataraman, Arvind" uniqKey="Venkataraman A" first="Arvind" last="Venkataraman">Arvind Venkataraman</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Zhou, Ziling" sort="Zhou, Ziling" uniqKey="Zhou Z" first="Ziling" last="Zhou">Ziling Zhou</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Zhou, Weidong" sort="Zhou, Weidong" uniqKey="Zhou W" first="Weidong" last="Zhou">Weidong Zhou</name><affiliation wicri:level="2"><nlm:affiliation>Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110</wicri:regionArea><placeName><region type="state">Virginie</region></placeName></affiliation></author><author><name sortKey="Zhu, Haiyan" sort="Zhu, Haiyan" uniqKey="Zhu H" first="Haiyan" last="Zhu">Haiyan Zhu</name><affiliation wicri:level="1"><nlm:affiliation>The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020</wicri:regionArea><placeName><settlement type="city">Tianjin</settlement></placeName></affiliation></author><author><name sortKey="Zhao, Li" sort="Zhao, Li" uniqKey="Zhao L" first="Li" last="Zhao">Li Zhao</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Sakai, Jiro" sort="Sakai, Jiro" uniqKey="Sakai J" first="Jiro" last="Sakai">Jiro Sakai</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Chen, Yuanyuan" sort="Chen, Yuanyuan" uniqKey="Chen Y" first="Yuanyuan" last="Chen">Yuanyuan Chen</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Pathophysiology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China; Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Pathophysiology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China; Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Ho, Ye Shih" sort="Ho, Ye Shih" uniqKey="Ho Y" first="Ye-Shih" last="Ho">Ye-Shih Ho</name><affiliation wicri:level="2"><nlm:affiliation>Institute of Environmental Health Sciences and Department of Biochemistry and Molecular Biology, Wayne State University, Detroit, MI 48201, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Environmental Health Sciences and Department of Biochemistry and Molecular Biology, Wayne State University, Detroit, MI 48201</wicri:regionArea><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Bajrami, Besnik" sort="Bajrami, Besnik" uniqKey="Bajrami B" first="Besnik" last="Bajrami">Besnik Bajrami</name><affiliation wicri:level="2"><nlm:affiliation>Mass Spectrometry Unit, Waters Corporation, Milford, MA 01757, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Mass Spectrometry Unit, Waters Corporation, Milford, MA 01757</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Xu, Bing" sort="Xu, Bing" uniqKey="Xu B" first="Bing" last="Xu">Bing Xu</name><affiliation wicri:level="2"><nlm:affiliation>Department of Chemistry, Brandeis University, 415 South Street MS015, Waltham, MA 02454, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Chemistry, Brandeis University, 415 South Street MS015, Waltham, MA 02454</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Silberstein, Leslie E" sort="Silberstein, Leslie E" uniqKey="Silberstein L" first="Leslie E" last="Silberstein">Leslie E. Silberstein</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Cheng, Tao" sort="Cheng, Tao" uniqKey="Cheng T" first="Tao" last="Cheng">Tao Cheng</name><affiliation wicri:level="1"><nlm:affiliation>The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020</wicri:regionArea><placeName><settlement type="city">Tianjin</settlement></placeName></affiliation></author><author><name sortKey="Xu, Yuanfu" sort="Xu, Yuanfu" uniqKey="Xu Y" first="Yuanfu" last="Xu">Yuanfu Xu</name><affiliation wicri:level="1"><nlm:affiliation>The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020</wicri:regionArea><placeName><settlement type="city">Tianjin</settlement></placeName></affiliation></author><author><name sortKey="Ke, Yuehai" sort="Ke, Yuehai" uniqKey="Ke Y" first="Yuehai" last="Ke">Yuehai Ke</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Luo, Hongbo R" sort="Luo, Hongbo R" uniqKey="Luo H" first="Hongbo R" last="Luo">Hongbo R. Luo</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA. Electronic address: hongbo.luo@childrens.harvard.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:28683316</idno><idno type="pmid">28683316</idno><idno type="doi">10.1016/j.celrep.2017.05.070</idno><idno type="pmc">PMC5758045</idno><idno type="wicri:Area/Main/Corpus">000325</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000325</idno><idno type="wicri:Area/Main/Curation">000325</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000325</idno><idno type="wicri:Area/Main/Exploration">000325</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Positive Regulation of Interleukin-1β Bioactivity by Physiological ROS-Mediated Cysteine S-Glutathionylation.</title><author><name sortKey="Zhang, Xue" sort="Zhang, Xue" uniqKey="Zhang X" first="Xue" last="Zhang">Xue Zhang</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Pathophysiology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China; Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA. Electronic address: zhangxue@zju.edu.cn.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Pathophysiology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China; Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Liu, Peng" sort="Liu, Peng" uniqKey="Liu P" first="Peng" last="Liu">Peng Liu</name><affiliation wicri:level="1"><nlm:affiliation>The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020</wicri:regionArea><placeName><settlement type="city">Tianjin</settlement></placeName></affiliation></author><author><name sortKey="Zhang, Christie" sort="Zhang, Christie" uniqKey="Zhang C" first="Christie" last="Zhang">Christie Zhang</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Chiewchengchol, Direkrit" sort="Chiewchengchol, Direkrit" uniqKey="Chiewchengchol D" first="Direkrit" last="Chiewchengchol">Direkrit Chiewchengchol</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Zhao, Fan" sort="Zhao, Fan" uniqKey="Zhao F" first="Fan" last="Zhao">Fan Zhao</name><affiliation wicri:level="1"><nlm:affiliation>The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020</wicri:regionArea><placeName><settlement type="city">Tianjin</settlement></placeName></affiliation></author><author><name sortKey="Yu, Hongbo" sort="Yu, Hongbo" uniqKey="Yu H" first="Hongbo" last="Yu">Hongbo Yu</name><affiliation wicri:level="2"><nlm:affiliation>Hematopathology, Flow Cytometry, Hematology, and Blood Bank Labs, VA Boston Healthcare System, West Roxbury, MA 02132, USA; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 01605, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Hematopathology, Flow Cytometry, Hematology, and Blood Bank Labs, VA Boston Healthcare System, West Roxbury, MA 02132, USA; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 01605</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Li, Jingyu" sort="Li, Jingyu" uniqKey="Li J" first="Jingyu" last="Li">Jingyu Li</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Kambara, Hiroto" sort="Kambara, Hiroto" uniqKey="Kambara H" first="Hiroto" last="Kambara">Hiroto Kambara</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Luo, Kate Y" sort="Luo, Kate Y" uniqKey="Luo K" first="Kate Y" last="Luo">Kate Y. Luo</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Venkataraman, Arvind" sort="Venkataraman, Arvind" uniqKey="Venkataraman A" first="Arvind" last="Venkataraman">Arvind Venkataraman</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Zhou, Ziling" sort="Zhou, Ziling" uniqKey="Zhou Z" first="Ziling" last="Zhou">Ziling Zhou</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Zhou, Weidong" sort="Zhou, Weidong" uniqKey="Zhou W" first="Weidong" last="Zhou">Weidong Zhou</name><affiliation wicri:level="2"><nlm:affiliation>Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110</wicri:regionArea><placeName><region type="state">Virginie</region></placeName></affiliation></author><author><name sortKey="Zhu, Haiyan" sort="Zhu, Haiyan" uniqKey="Zhu H" first="Haiyan" last="Zhu">Haiyan Zhu</name><affiliation wicri:level="1"><nlm:affiliation>The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020</wicri:regionArea><placeName><settlement type="city">Tianjin</settlement></placeName></affiliation></author><author><name sortKey="Zhao, Li" sort="Zhao, Li" uniqKey="Zhao L" first="Li" last="Zhao">Li Zhao</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Sakai, Jiro" sort="Sakai, Jiro" uniqKey="Sakai J" first="Jiro" last="Sakai">Jiro Sakai</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Chen, Yuanyuan" sort="Chen, Yuanyuan" uniqKey="Chen Y" first="Yuanyuan" last="Chen">Yuanyuan Chen</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Pathophysiology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China; Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Pathophysiology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China; Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Ho, Ye Shih" sort="Ho, Ye Shih" uniqKey="Ho Y" first="Ye-Shih" last="Ho">Ye-Shih Ho</name><affiliation wicri:level="2"><nlm:affiliation>Institute of Environmental Health Sciences and Department of Biochemistry and Molecular Biology, Wayne State University, Detroit, MI 48201, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Environmental Health Sciences and Department of Biochemistry and Molecular Biology, Wayne State University, Detroit, MI 48201</wicri:regionArea><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Bajrami, Besnik" sort="Bajrami, Besnik" uniqKey="Bajrami B" first="Besnik" last="Bajrami">Besnik Bajrami</name><affiliation wicri:level="2"><nlm:affiliation>Mass Spectrometry Unit, Waters Corporation, Milford, MA 01757, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Mass Spectrometry Unit, Waters Corporation, Milford, MA 01757</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Xu, Bing" sort="Xu, Bing" uniqKey="Xu B" first="Bing" last="Xu">Bing Xu</name><affiliation wicri:level="2"><nlm:affiliation>Department of Chemistry, Brandeis University, 415 South Street MS015, Waltham, MA 02454, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Chemistry, Brandeis University, 415 South Street MS015, Waltham, MA 02454</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Silberstein, Leslie E" sort="Silberstein, Leslie E" uniqKey="Silberstein L" first="Leslie E" last="Silberstein">Leslie E. Silberstein</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Cheng, Tao" sort="Cheng, Tao" uniqKey="Cheng T" first="Tao" last="Cheng">Tao Cheng</name><affiliation wicri:level="1"><nlm:affiliation>The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020</wicri:regionArea><placeName><settlement type="city">Tianjin</settlement></placeName></affiliation></author><author><name sortKey="Xu, Yuanfu" sort="Xu, Yuanfu" uniqKey="Xu Y" first="Yuanfu" last="Xu">Yuanfu Xu</name><affiliation wicri:level="1"><nlm:affiliation>The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020</wicri:regionArea><placeName><settlement type="city">Tianjin</settlement></placeName></affiliation></author><author><name sortKey="Ke, Yuehai" sort="Ke, Yuehai" uniqKey="Ke Y" first="Yuehai" last="Ke">Yuehai Ke</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Luo, Hongbo R" sort="Luo, Hongbo R" uniqKey="Luo H" first="Hongbo R" last="Luo">Hongbo R. Luo</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA. Electronic address: hongbo.luo@childrens.harvard.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author></analytic><series><title level="j">Cell reports</title><idno type="eISSN">2211-1247</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Motifs (MeSH)</term><term>Animals (MeSH)</term><term>Bone Marrow Cells (metabolism)</term><term>Cysteine (metabolism)</term><term>Glutaredoxins (metabolism)</term><term>Glutathione (metabolism)</term><term>Interleukin-1beta (chemistry)</term><term>Interleukin-1beta (metabolism)</term><term>Male (MeSH)</term><term>Mice (MeSH)</term><term>Mice, Inbred C57BL (MeSH)</term><term>Protein Processing, Post-Translational (MeSH)</term><term>Reactive Oxygen Species (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term><term>Cellules de la moelle osseuse (métabolisme)</term><term>Cystéine (métabolisme)</term><term>Espèces réactives de l'oxygène (métabolisme)</term><term>Glutarédoxines (métabolisme)</term><term>Glutathion (métabolisme)</term><term>Interleukine-1 bêta (composition chimique)</term><term>Interleukine-1 bêta (métabolisme)</term><term>Maturation post-traductionnelle des protéines (MeSH)</term><term>Motifs d'acides aminés (MeSH)</term><term>Mâle (MeSH)</term><term>Souris (MeSH)</term><term>Souris de lignée C57BL (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Interleukin-1beta</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cysteine</term><term>Glutaredoxins</term><term>Glutathione</term><term>Interleukin-1beta</term><term>Reactive Oxygen Species</term></keywords><keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr"><term>Interleukine-1 bêta</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Bone Marrow Cells</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cellules de la moelle osseuse</term><term>Cystéine</term><term>Espèces réactives de l'oxygène</term><term>Glutarédoxines</term><term>Glutathion</term><term>Interleukine-1 bêta</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Motifs</term><term>Animals</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Protein Processing, Post-Translational</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Maturation post-traductionnelle des protéines</term><term>Motifs d'acides aminés</term><term>Mâle</term><term>Souris</term><term>Souris de lignée C57BL</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Reactive oxygen species (ROS)-induced cysteine S-glutathionylation is an important posttranslational modification (PTM) that controls a wide range of intracellular protein activities. However, whether physiological ROS can modulate the function of extracellular components via S-glutathionylation is unknown. Using a screening approach, we identified ROS-mediated cysteine S-glutathionylation on several extracellular cytokines. Glutathionylation of the highly conserved Cys-188 in IL-1β positively regulates its bioactivity by preventing its ROS-induced irreversible oxidation, including sulfinic acid and sulfonic acid formation. We show this mechanism protects IL-1β from deactivation by ROS in an in vivo system of irradiation-induced bone marrow (BM) injury. Glutaredoxin 1 (Grx1), an enzyme that catalyzes deglutathionylation, was present and active in the extracellular space in serum and the BM, physiologically regulating IL-1β glutathionylation and bioactivity. Collectively, we identify cysteine S-glutathionylation as a cytokine regulatory mechanism that could be a therapeutic target in the treatment of various infectious and inflammatory diseases.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28683316</PMID><DateCompleted><Year>2018</Year><Month>03</Month><Day>26</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">2211-1247</ISSN><JournalIssue CitedMedium="Internet"><Volume>20</Volume><Issue>1</Issue><PubDate><Year>2017</Year><Month>07</Month><Day>05</Day></PubDate></JournalIssue><Title>Cell reports</Title><ISOAbbreviation>Cell Rep</ISOAbbreviation></Journal><ArticleTitle>Positive Regulation of Interleukin-1β Bioactivity by Physiological ROS-Mediated Cysteine S-Glutathionylation.</ArticleTitle><Pagination><MedlinePgn>224-235</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S2211-1247(17)30727-1</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.celrep.2017.05.070</ELocationID><Abstract><AbstractText>Reactive oxygen species (ROS)-induced cysteine S-glutathionylation is an important posttranslational modification (PTM) that controls a wide range of intracellular protein activities. However, whether physiological ROS can modulate the function of extracellular components via S-glutathionylation is unknown. Using a screening approach, we identified ROS-mediated cysteine S-glutathionylation on several extracellular cytokines. Glutathionylation of the highly conserved Cys-188 in IL-1β positively regulates its bioactivity by preventing its ROS-induced irreversible oxidation, including sulfinic acid and sulfonic acid formation. We show this mechanism protects IL-1β from deactivation by ROS in an in vivo system of irradiation-induced bone marrow (BM) injury. Glutaredoxin 1 (Grx1), an enzyme that catalyzes deglutathionylation, was present and active in the extracellular space in serum and the BM, physiologically regulating IL-1β glutathionylation and bioactivity. Collectively, we identify cysteine S-glutathionylation as a cytokine regulatory mechanism that could be a therapeutic target in the treatment of various infectious and inflammatory diseases.</AbstractText><CopyrightInformation>Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Xue</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Pathology and Pathophysiology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China; Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA. Electronic address: zhangxue@zju.edu.cn.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Peng</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Christie</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chiewchengchol</LastName><ForeName>Direkrit</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Fan</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yu</LastName><ForeName>Hongbo</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Hematopathology, Flow Cytometry, Hematology, and Blood Bank Labs, VA Boston Healthcare System, West Roxbury, MA 02132, USA; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 01605, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Jingyu</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kambara</LastName><ForeName>Hiroto</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Luo</LastName><ForeName>Kate Y</ForeName><Initials>KY</Initials><AffiliationInfo><Affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Venkataraman</LastName><ForeName>Arvind</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhou</LastName><ForeName>Ziling</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhou</LastName><ForeName>Weidong</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhu</LastName><ForeName>Haiyan</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Li</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sakai</LastName><ForeName>Jiro</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Yuanyuan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Pathology and Pathophysiology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China; Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ho</LastName><ForeName>Ye-Shih</ForeName><Initials>YS</Initials><AffiliationInfo><Affiliation>Institute of Environmental Health Sciences and Department of Biochemistry and Molecular Biology, Wayne State University, Detroit, MI 48201, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bajrami</LastName><ForeName>Besnik</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Mass Spectrometry Unit, Waters Corporation, Milford, MA 01757, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Bing</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Chemistry, Brandeis University, 415 South Street MS015, Waltham, MA 02454, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Silberstein</LastName><ForeName>Leslie E</ForeName><Initials>LE</Initials><AffiliationInfo><Affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cheng</LastName><ForeName>Tao</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Yuanfu</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ke</LastName><ForeName>Yuehai</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Luo</LastName><ForeName>Hongbo R</ForeName><Initials>HR</Initials><AffiliationInfo><Affiliation>Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA. Electronic address: hongbo.luo@childrens.harvard.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 GM076084</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI103142</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 HL092020</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P01 HL095489</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI076471</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType 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first="Yuanyuan" last="Chen">Yuanyuan Chen</name><name sortKey="Chiewchengchol, Direkrit" sort="Chiewchengchol, Direkrit" uniqKey="Chiewchengchol D" first="Direkrit" last="Chiewchengchol">Direkrit Chiewchengchol</name><name sortKey="Ho, Ye Shih" sort="Ho, Ye Shih" uniqKey="Ho Y" first="Ye-Shih" last="Ho">Ye-Shih Ho</name><name sortKey="Kambara, Hiroto" sort="Kambara, Hiroto" uniqKey="Kambara H" first="Hiroto" last="Kambara">Hiroto Kambara</name><name sortKey="Ke, Yuehai" sort="Ke, Yuehai" uniqKey="Ke Y" first="Yuehai" last="Ke">Yuehai Ke</name><name sortKey="Li, Jingyu" sort="Li, Jingyu" uniqKey="Li J" first="Jingyu" last="Li">Jingyu Li</name><name sortKey="Luo, Hongbo R" sort="Luo, Hongbo R" uniqKey="Luo H" first="Hongbo R" last="Luo">Hongbo R. 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