Deciphering the safeguarding role of cysteine residues in p53 against H2O2-induced oxidation using high-resolution native mass spectrometry
Abstract The transcription factor p53 is exquisitely sensitive and selective to a broad variety of cellular environments. Several studies have reported that oxidative stress weakens the p53-DNA binding affinity for certain promoters depending on the oxidation mechanism. Despite this body of work, th...
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| Format: | Article |
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Nature Portfolio
2025-01-01
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| Series: | Communications Chemistry |
| Online Access: | https://doi.org/10.1038/s42004-024-01395-w |
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| author | Manuel David Peris-Díaz Artur Krężel Perdita Barran |
| author_facet | Manuel David Peris-Díaz Artur Krężel Perdita Barran |
| author_sort | Manuel David Peris-Díaz |
| collection | DOAJ |
| description | Abstract The transcription factor p53 is exquisitely sensitive and selective to a broad variety of cellular environments. Several studies have reported that oxidative stress weakens the p53-DNA binding affinity for certain promoters depending on the oxidation mechanism. Despite this body of work, the precise mechanisms by which the physiologically relevant DNA-p53 tetramer complex senses cellular stresses caused by H2O2 are still unknown. Here, we employed native mass spectrometry (MS) and ion mobility (IM)-MS coupled to chemical labelling and H2O2-induced oxidation to examine the mechanism of redox regulation of the p53-p21 complex. Our approach has found that two reactive cysteines in p53 protect against H2O2-induced oxidation by forming reversible sulfenates. |
| format | Article |
| id | doaj-art-23c637bc329c46e2bd346655b085906b |
| institution | Kabale University |
| issn | 2399-3669 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Chemistry |
| spelling | doaj-art-23c637bc329c46e2bd346655b085906b2025-01-19T12:13:12ZengNature PortfolioCommunications Chemistry2399-36692025-01-018111410.1038/s42004-024-01395-wDeciphering the safeguarding role of cysteine residues in p53 against H2O2-induced oxidation using high-resolution native mass spectrometryManuel David Peris-Díaz0Artur Krężel1Perdita Barran2Michael Barber Centre for Collaborative Mass Spectrometry, Manchester Institute of BiotechnologyDepartment of Chemical Biology, Faculty of Biotechnology, University of Wrocław, F. Joliot-Curie 14aMichael Barber Centre for Collaborative Mass Spectrometry, Manchester Institute of BiotechnologyAbstract The transcription factor p53 is exquisitely sensitive and selective to a broad variety of cellular environments. Several studies have reported that oxidative stress weakens the p53-DNA binding affinity for certain promoters depending on the oxidation mechanism. Despite this body of work, the precise mechanisms by which the physiologically relevant DNA-p53 tetramer complex senses cellular stresses caused by H2O2 are still unknown. Here, we employed native mass spectrometry (MS) and ion mobility (IM)-MS coupled to chemical labelling and H2O2-induced oxidation to examine the mechanism of redox regulation of the p53-p21 complex. Our approach has found that two reactive cysteines in p53 protect against H2O2-induced oxidation by forming reversible sulfenates.https://doi.org/10.1038/s42004-024-01395-w |
| spellingShingle | Manuel David Peris-Díaz Artur Krężel Perdita Barran Deciphering the safeguarding role of cysteine residues in p53 against H2O2-induced oxidation using high-resolution native mass spectrometry Communications Chemistry |
| title | Deciphering the safeguarding role of cysteine residues in p53 against H2O2-induced oxidation using high-resolution native mass spectrometry |
| title_full | Deciphering the safeguarding role of cysteine residues in p53 against H2O2-induced oxidation using high-resolution native mass spectrometry |
| title_fullStr | Deciphering the safeguarding role of cysteine residues in p53 against H2O2-induced oxidation using high-resolution native mass spectrometry |
| title_full_unstemmed | Deciphering the safeguarding role of cysteine residues in p53 against H2O2-induced oxidation using high-resolution native mass spectrometry |
| title_short | Deciphering the safeguarding role of cysteine residues in p53 against H2O2-induced oxidation using high-resolution native mass spectrometry |
| title_sort | deciphering the safeguarding role of cysteine residues in p53 against h2o2 induced oxidation using high resolution native mass spectrometry |
| url | https://doi.org/10.1038/s42004-024-01395-w |
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