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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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
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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| Summary: | 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. |
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| ISSN: | 2399-3669 |