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Updated: Mar 29, 2026
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Mutant p53: Multiple Mechanisms Define Biologic Activity in Cancer
Michael Paul Kim1, Yun Zhang2, Guillermina Lozano2
1Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center , Houston, TX , USA ; Department of Genetics, The University of Texas MD Anderson Cancer Center , Houston, TX , USA.
Abstract:
The functional importance of p53 as a tumor suppressor gene is evident through its pervasiveness in cancer biology. The p53 gene is the most commonly altered gene in human cancer; however, not all genetic alterations are biologically equivalent. The majority of alterations involve p53 missense mutations that result in the production of mutant p53 proteins. Such mutant p53 proteins lack normal p53 function and may concomitantly gain novel functions, often with deleterious effects. Here, we review characterized mechanisms of mutant p53 gain of function in various model systems. In addition, we review mutant p53 addiction as emerging evidence suggests that tumors may depend on sustained mutant p53 activity for continued growth. We also discuss the role of p53 in stromal elements and their contribution to tumor initiation and progression. Lastly, current genetic mouse models of mutant p53 in various organ systems are reviewed and their limitations discussed.
Insights
Mutant p53 proteins, arising from common genetic alterations, can gain harmful functions and drive tumor growth. Tumors may become dependent on these mutant p53 activities for survival and progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The p53 gene is a critical tumor suppressor frequently altered in human cancers.
- Most alterations involve missense mutations, leading to non-functional or gain-of-function mutant p53 proteins.
Purpose of the Study:
- To review mechanisms of mutant p53 gain-of-function (GOF).
- To discuss mutant p53 addiction in cancer.
- To explore p53's role in stromal elements and evaluate mouse models.
Main Methods:
- Literature review of characterized mechanisms.
- Analysis of emerging evidence on mutant p53 addiction.
- Discussion of p53's role in tumor stroma.
- Review of genetic mouse models.
Main Results:
- Mutant p53 proteins exhibit diverse GOF mechanisms.
- Emerging evidence indicates tumor dependence on sustained mutant p53 activity.
- p53 in stromal cells contributes to tumor initiation and progression.
Conclusions:
- Mutant p53 GOF and addiction are significant in cancer biology.
- Understanding these mechanisms is crucial for therapeutic strategies.
- Genetic mouse models are valuable but have limitations.
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