Deubiquitinases as a Signaling Target of Oxidative Stress
Deubiquitinating enzymes (DUBs) constitute a large family of cysteine proteases that have a broad impact on numerous biological and pathological processes, including the regulation of genomic stability. DUBs are often assembled onto multiprotein complexes to assist in their localization and substrat...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2012-12-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124712003920 |
| _version_ | 1811298588626518016 |
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| author | Xiomaris M. Cotto-Rios Miklós Békés Jessica Chapman Beatrix Ueberheide Tony T. Huang |
| author_facet | Xiomaris M. Cotto-Rios Miklós Békés Jessica Chapman Beatrix Ueberheide Tony T. Huang |
| author_sort | Xiomaris M. Cotto-Rios |
| collection | DOAJ |
| description | Deubiquitinating enzymes (DUBs) constitute a large family of cysteine proteases that have a broad impact on numerous biological and pathological processes, including the regulation of genomic stability. DUBs are often assembled onto multiprotein complexes to assist in their localization and substrate selection, yet it remains unclear how the enzymatic activity of DUBs is modulated by intracellular signals. Herein, we show that bursts of reactive oxygen species (ROS) reversibly inactivate DUBs through the oxidation of the catalytic cysteine residue. Importantly, USP1, a key regulator of genomic stability, is reversibly inactivated upon oxidative stress. This, in part, explains the rapid nature of PCNA monoubiquitination-dependent DNA damage tolerance in response to oxidative DNA damage in replicating cells. We propose that DUBs of the cysteine protease family act as ROS sensors in human cells and that ROS-mediated DUB inactivation is a critical mechanism for fine-tuning stress-activated signaling pathways. |
| first_indexed | 2024-04-13T06:21:29Z |
| format | Article |
| id | doaj.art-14d9f84402544c939e73141b12618d81 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T06:21:29Z |
| publishDate | 2012-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-14d9f84402544c939e73141b12618d812022-12-22T02:58:36ZengElsevierCell Reports2211-12472012-12-01261475148410.1016/j.celrep.2012.11.011Deubiquitinases as a Signaling Target of Oxidative StressXiomaris M. Cotto-Rios0Miklós Békés1Jessica Chapman2Beatrix Ueberheide3Tony T. Huang4Department of Biochemistry & Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USADepartment of Biochemistry & Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USADepartment of Biochemistry & Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USADepartment of Biochemistry & Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USADepartment of Biochemistry & Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USADeubiquitinating enzymes (DUBs) constitute a large family of cysteine proteases that have a broad impact on numerous biological and pathological processes, including the regulation of genomic stability. DUBs are often assembled onto multiprotein complexes to assist in their localization and substrate selection, yet it remains unclear how the enzymatic activity of DUBs is modulated by intracellular signals. Herein, we show that bursts of reactive oxygen species (ROS) reversibly inactivate DUBs through the oxidation of the catalytic cysteine residue. Importantly, USP1, a key regulator of genomic stability, is reversibly inactivated upon oxidative stress. This, in part, explains the rapid nature of PCNA monoubiquitination-dependent DNA damage tolerance in response to oxidative DNA damage in replicating cells. We propose that DUBs of the cysteine protease family act as ROS sensors in human cells and that ROS-mediated DUB inactivation is a critical mechanism for fine-tuning stress-activated signaling pathways.http://www.sciencedirect.com/science/article/pii/S2211124712003920 |
| spellingShingle | Xiomaris M. Cotto-Rios Miklós Békés Jessica Chapman Beatrix Ueberheide Tony T. Huang Deubiquitinases as a Signaling Target of Oxidative Stress Cell Reports |
| title | Deubiquitinases as a Signaling Target of Oxidative Stress |
| title_full | Deubiquitinases as a Signaling Target of Oxidative Stress |
| title_fullStr | Deubiquitinases as a Signaling Target of Oxidative Stress |
| title_full_unstemmed | Deubiquitinases as a Signaling Target of Oxidative Stress |
| title_short | Deubiquitinases as a Signaling Target of Oxidative Stress |
| title_sort | deubiquitinases as a signaling target of oxidative stress |
| url | http://www.sciencedirect.com/science/article/pii/S2211124712003920 |
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