Deciphering the role of post-translational modifications in p53 regulation with protein semisynthesis

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• Dr. Manuel Muller
• Wednesday 21 April 2021, 10:30-11:30
• https://zoom.us/j/95477079823.

If you have a question about this talk, please contact Anne Jacobs.

The tumour suppressor protein p53 orchestrates the response to cell damage and thus plays a central role in preventing cancer. p53 is tightly regulated by post-translational modifications (PTMs). The precise mechanisms through which p53 PTMs operate are difficult to elucidate due to the complexity of p53 signalling and challenges associated with preparing site-specifically modified p53 for in vitro studies. To address these issues, we have developed a protein semi-synthesis strategy to access p53 in defined PTM states. Using such ‘designer’ phospho-p53 variants we have probed the mechanism of p53 activation through phosphorylation in vitro. Moreover, we found that a spontaneous protein backbone modification, the rearrangement of an asparagine to an isoaspartate residue, reconfigures p53’s binding partner specificity, which suggests that p53 could act as a molecular time bomb. Given the importance of PTMs in p53 signalling, we believe that our chemistry-driven approach will contribute greatly to a mechanistic understanding of how this protein makes cellular life and death decisions.

This talk is part of the Biophysical Seminars series.

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• All Talks (aka the CURE list)
• Biophysical Seminar Series 2016/17
• Biophysical Seminars
• Department of Chemistry
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• School of Physical Sciences
• https://zoom.us/j/95477079823

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