Dissecting p53 signaling with Chemical Biology

Manuel Mueller (primary)
King's College London
Mahvash Tavassoli (secondary)
King's College London


The tumor suppressor protein p53 plays a central role in orchestrating the cellular response to genotoxic damage. Specifically, p53 can induce DNA damage repair processes or in extreme cases initiate controlled cell death (apoptosis). Mutations in p53 are frequently found in cancers, highlighting p53’s importance in maintaining healthy cell populations. p53 is tightly controlled by diverse post-translational modifications, but the molecular details of how individual modification and combinations thereof contribute to p53 activity are poorly understood. This project uses synthetic protein chemistry (Müller lab) to investigate the biological outputs (Tavassoli lab) of specific p53 modifications.


1 Hafner, A et al. (2019) The multiple mechanisms that regulate p53 activity and cell fate. Nature Reviews Mol. Cell Biol. 20: 199.
2 Semisynthetic ‘designer’ p53 sheds light on a phosphorylation-acetylation relay. Margiola S, Gerecht K, Müller MM. Chem Sci 2021 in press. https://doi.org/10.1039/D1SC00396H
3 Müller, M and Muir, T. (2015) Histones: At the Crossroads of Peptide and Protein Chemistry. Chemical Reviews115: 2296.
4 Bergamaschi, D et al. (2003) p53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis. Cancer Cell. 3:387.
5 Hooper, C et al. (2007) p53 is upregulated in Alzheimer’s disease and induces tau phosphorylation in HEK293a cells. Neurosci. Lett. 418:34.

Genes, development and STEM* approaches to biology
Area of Biology
Cell BiologyChemical Biology
Techniques & Approaches
BiochemistryBiophysicsChemistryMicroscopy / ElectrophysiologyMolecular Biology