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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Mutant p53 gain-of-function in cancer
1Department of Molecular Cell Biology, The Weizmann Institute, Rehovot 76100, Israel. moshe.oren@weizmann.ac.il
Abstract:
In its wild-type form, p53 is a major tumor suppressor whose function is critical for protection against cancer. Many human tumors carry missense mutations in the TP53 gene, encoding p53. Typically, the affected tumor cells accumulate excessive amounts of the mutant p53 protein. Various lines of evidence indicate that, in addition to abrogating the tumor suppressor functions of wild-type p53, the common types of cancer-associated p53 mutations also endow the mutant protein with new activities that can contribute actively to various stages of tumor progression and to increased resistance to anticancer treatments. Collectively, these activities are referred to as mutant p53 gain-of-function. This article addresses the biological manifestations of mutant p53 gain-of-function, the underlying molecular mechanisms, and their possible clinical implications.
Insights
Mutant p53 protein, often found in human tumors, gains new cancer-promoting activities. These gain-of-function mutations in the TP53 gene contribute to tumor progression and treatment resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The p53 protein (encoded by the TP53 gene) is a critical tumor suppressor.
- Missense mutations in TP53 are common in human cancers.
- Mutant p53 protein accumulates in tumor cells, losing wild-type tumor suppressor functions.
Purpose of the Study:
- To review the biological effects of mutant p53 gain-of-function.
- To explore the molecular mechanisms driving these new activities.
- To discuss potential clinical implications of mutant p53 in cancer.
Main Methods:
- This review synthesizes existing research findings.
- It examines evidence from various studies on p53 mutations.
- The focus is on biological manifestations and molecular underpinnings.
Main Results:
- Mutant p53 exhibits gain-of-function activities beyond loss of tumor suppression.
- These activities promote tumor progression and metastasis.
- Mutant p53 confers resistance to conventional anticancer therapies.
Conclusions:
- Mutant p53 gain-of-function is a significant factor in cancer development and progression.
- Understanding these mechanisms may reveal new therapeutic strategies.
- Targeting mutant p53 could offer novel approaches to cancer treatment.
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