Related Experiment Video
Updated: Sep 26, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
p53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis
Daniele Bergamaschi1, Milena Gasco, Louise Hiller
1Ludwig Institute for Cancer Research, Imperial College Faculty of Medicine, St. Mary's Campus, London, England.
Abstract:
Intact p73 function is shown to be an important determinant of cellular sensitivity to anticancer agents. Inhibition of p73 function by dominant-negative proteins or by mutant p53 abrogates apoptosis and cytotoxicity induced by these agents. A polymorphism encoding either arginine (72R) or proline (72P) at codon 72 of p53 influences inhibition of p73 by a range of p53 mutants identified in squamous cancers. Clinical response following cisplatin-based chemo-radiotherapy for advanced head and neck cancer is influenced by this polymorphism, cancers expressing 72R mutants having lower response rates than those expressing 72P mutants. Polymorphism in p53 may influence individual responsiveness to cancer therapy.
Insights
The p53 gene polymorphism at codon 72 affects how well cancer cells respond to chemotherapy. The 72R variant is linked to lower treatment response rates in head and neck cancers.
Area of Science:
- Molecular biology
- Cancer research
- Genetics
Background:
- Intact p73 protein function is crucial for cellular sensitivity to anticancer drugs.
- Inhibiting p73 function, through dominant-negative proteins or mutant p53, reduces apoptosis and cytotoxicity.
- Mutant p53 proteins can inhibit p73 function.
Purpose of the Study:
- To investigate the role of p53 codon 72 polymorphism in p73 inhibition.
- To determine the clinical relevance of this polymorphism in head and neck cancer treatment response.
Main Methods:
- Analysis of p53 codon 72 polymorphism (arginine 72R vs. proline 72P).
- Assessment of p53 mutants' ability to inhibit p73 function.
- Correlation of p53 polymorphism with clinical response to cisplatin-based chemo-radiotherapy in advanced head and neck cancer patients.
Main Results:
- A polymorphism in p53 at codon 72 influences p73 inhibition by various p53 mutants found in squamous cancers.
- Cancers with 72R p53 mutants showed lower response rates to cisplatin-based chemo-radiotherapy compared to those with 72P mutants.
- This suggests a differential impact of p53 variants on treatment efficacy.
Conclusions:
- The p53 codon 72 polymorphism plays a role in modulating p73 function and cellular response to anticancer agents.
- This genetic variation may influence individual patient responsiveness to chemo-radiotherapy, particularly in head and neck cancers.
- Understanding p53 polymorphism could aid in personalized cancer treatment strategies.
Related Concept Videos
Abnormal Proliferation
DNA Damage Can Stall the Cell Cycle
DNA Damage can Stall the Cell Cycle
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Negative Regulator Molecules
The Intrinsic Apoptotic Pathway

