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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Mutant p53 proteins: between loss and gain of function
Sabrina Strano1, Stefania Dell'Orso, Adriana Maria Mongiovi
1Department of Experimental Oncology, Regina Elena Cancer Institute, 00158 Rome, Italy.
Abstract:
Cancer might result from both the aberrant activation of genes, whose physiological tuning is essential for the life of a normal cell, and the inactivation of tumor suppressor genes, whose main job is to preserve the integrity of cell genome. Among the latter, p53 is considered a key tumor suppressor gene that is inactivated mainly by missense mutations in half of human cancers. It is becoming increasingly clear that the resulting mutant p53 proteins gain oncogenic properties favoring the insurgence, the maintenance, and the spreading of malignant tumors. In this review, we mainly discuss the molecular mechanisms underlying gain of function of human tumor-derived p53 mutants, their impact on the chemoresistance and the prognosis of human tumors, with a special focus on head and neck cancers, and the perspectives of treating tumors through the manipulation of mutant p53 proteins.
Insights
Mutant p53 proteins, arising from tumor suppressor gene inactivation, gain oncogenic properties that drive cancer progression. This review explores their mechanisms, impact on chemoresistance and prognosis, and therapeutic strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cancer development involves gene activation and tumor suppressor gene inactivation.
- The p53 gene, a critical tumor suppressor, is frequently inactivated by missense mutations in human cancers.
- Mutant p53 proteins acquire oncogenic functions, promoting tumor insurgence, maintenance, and metastasis.
Purpose of the Study:
- To review the molecular mechanisms of gain-of-function mutations in human tumor-derived p53.
- To analyze the impact of mutant p53 on chemoresistance and prognosis in human cancers, particularly head and neck cancers.
- To discuss therapeutic strategies targeting mutant p53 proteins.
Main Methods:
- Literature review focusing on molecular mechanisms of p53 mutations.
- Analysis of studies investigating p53 mutant protein function.
- Examination of clinical data on chemoresistance and prognosis related to p53 mutations.
Main Results:
- Mutant p53 proteins exhibit gain-of-function activities, contributing to oncogenesis.
- p53 mutations are associated with altered chemoresistance and poorer prognosis in various cancers.
- Head and neck cancers show a significant impact of mutant p53 on clinical outcomes.
Conclusions:
- Understanding mutant p53 gain-of-function mechanisms is crucial for cancer therapy.
- Targeting mutant p53 offers a promising therapeutic avenue for cancer treatment.
- Further research into manipulating mutant p53 holds potential for improving patient outcomes.
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