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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
An overview of the functions of p53 and drugs acting either on wild- or mutant-type p53
Yongmi Huang1, Zhihao Jiao1, Yuqing Fu1
1Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, PR China.
Abstract:
TP53, also known as the "guardian of the genome," is an important tumor suppressor gene. It is encoded by the human genome and is associated with the development of diverse cancers. The p53 protein, encoded by TP53, functions in the cell to monitor DNA damage and prompts the cell to respond appropriately. When DNA is damaged, p53 halts the cell cycle, allowing cells to enter the repair state. If the repair is ineffective, p53 induces cell death via apoptosis. This prevents DNA damage transmission during cell division and reduces cancer risk. However, the p53 gene mutation compromises its function. This leads to the inability of cells to respond properly to DNA damage, which may result in cancer development. Mutations in p53 are widespread in diverse cancers, especially highly prevalent cancers, including breast, colon, and lung cancers. Despite the association between p53 mutations and cancer, researchers have discovered drugs and treatments that may reactivate mutated p53 function. Therefore, p53 remains an important area of research in cancer treatment and holds promise as a new direction for cancer therapy. In summary, TP53 is a vital tumor suppressor gene responsible for monitoring DNA damage and prompting cells to respond appropriately. This article summarizes drugs related to p53 and diverse strategies for discovering drugs that act on either wide or mutant p53. Herein, p53 is categorized into two types: wild and mutant type. Drugs are also classified according to diverse treatment strategies, enabling readers to differentiate between the two types of p53 and aiding in selecting the appropriate research direction. Additionally, this review offers a valuable reference for drug design.
Insights
The TP53 gene, or tumor protein 53, acts as a guardian of the genome. Research explores drugs to reactivate its function, offering new cancer treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The TP53 gene encodes the p53 protein, a critical tumor suppressor.
- p53 monitors DNA damage, halting cell cycles for repair or inducing apoptosis.
- TP53 mutations compromise these functions, contributing to various cancers.
Purpose of the Study:
- To review drugs targeting wild-type and mutant TP53.
- To summarize diverse strategies for discovering p53-acting drugs.
- To aid researchers in selecting appropriate research directions for p53 drug development.
Main Methods:
- Literature review of TP53-related drugs and cancer research.
- Categorization of p53 into wild and mutant types.
- Classification of drugs based on treatment strategies.
Main Results:
- TP53 mutations are prevalent in major cancers like breast, colon, and lung.
- Emerging drugs show potential in reactivating mutated p53.
- p53 remains a key target for novel cancer therapies.
Conclusions:
- TP53 is a vital gene in cancer suppression.
- Targeting wild-type and mutant p53 represents a promising therapeutic avenue.
- This review provides a framework for p53-focused drug design and research.
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