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<p>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 H<sub>2</sub>O<sub>2</sub> are still unknown. Here, we employed native mass spectrometry (MS) and ion mobility (IM)-MS coupled to chemical labelling and H<sub>2</sub>O<sub>2</sub>-induced oxidation to examine the mechanism of redox regulation of the p53-<i>p21</i> complex. Our approach has found that two reactive cysteines in p53 protect against H<sub>2</sub>O<sub>2</sub>-induced oxidation by forming reversible sulfenates.</p><p></p>

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Deciphering the safeguarding role of cysteine residues in p53 against H2O2-induced oxidation using high-resolution native mass spectrometry

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  • 发表日期：

    2025年1月15日

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  • Manuel David Peris-Díaz,
  • Artur Krężel,
  • Perdita Barran

摘要

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.