Andreas C. Joerger

Jan 9, 2025 | nature.com | Philipp Münick |Alexander Strubel |Dimitrios-Ilias Balourdas |Julianne Funk |Marcel Tuppi |Busra Yuksel | +4 more

AbstractInfection of cells with high-risk strains of the human papillomavirus (HPV) causes cancer in various types of epithelial tissue. HPV infections are responsible for ~4.5% of all cancers worldwide. Tumorigenesis is based on the inactivation of key cellular control mechanisms by the viral proteins E6 and E7. The HPV E6 protein interacts with the cellular E3 ligase E6AP, and this complex binds to the p53 DNA-binding domain, which results in degradation of p53.

Jan 7, 2025 | nature.com | Julianne Funk |Pascal Hunold |Dimitrios-Ilias Balourdas |Marek Bartkuhn |Rajkumar Savai |Thierry Soussi | +2 more

AbstractThe mutational landscape of TP53, a tumor suppressor mutated in about half of all cancers, includes over 2,000 known missense mutations. To fully leverage TP53 mutation status for personalized medicine, a thorough understanding of the functional diversity of these mutations is essential. We conducted a deep mutational scan using saturation genome editing with CRISPR-mediated homology-directed repair to engineer 9,225 TP53 variants in cancer cells.

Oct 22, 2024 | nature.com | Andreas C. Joerger |Thorsten Stiewe

AbstractThe transcription factor p53 plays a key role in the cellular defense against cancer development. It is inactivated in virtually every tumor, and in every second tumor this inactivation is due to a mutation in the TP53 gene. In this perspective, we show that this diverse mutational spectrum is unique among all other cancer-associated proteins and discuss what drives the selection of TP53 mutations in cancer.