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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
The TP53 fertility network
Diego d'Avila Paskulin1, Vanessa Rodrigues Paixão-Côrtes, Pierre Hainaut
1Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. ; Laboratório de Medicina Genômica, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
Abstract:
The TP53 gene, first described in 1979, was identified as a tumor suppressor gene in 1989, when it became clear that its product, the p53 nuclear phosphoprotein, was frequently inactivated in many different forms of cancers. Nicknamed "guardian of the genome", TP53 occupies a central node in stress response networks. The p53 protein has a key role as transcription factor in limiting oncogenesis through several growth suppressive functions, such as initiating apoptosis, senescence, or cell cycle arrest. The p53 protein is directly inactivated in about 50% of all tumors as a result of somatic gene mutations or deletions, and over 80% of tumors demonstrate dysfunctional p53 signaling. Beyond the undeniable importance of p53 as a tumor suppressor, an increasing number of new functions for p53 have been reported, including its ability to regulate energy metabolism, to control autophagy, and to participate in various aspects of differentiation and development. Recently, studies on genetic variations in TP53 among different populations have led to the notion that the p53 protein might play an important role in regulating fertility. This review summarizes current knowledge on the basic functions of different genes of the TP53 family and TP53 pathway with respect to fertility. We also provide original analyses based on genomic and genotype databases, providing further insights into the possible roles of the TP53 pathway in human reproduction.
Insights
The TP53 gene, known as the guardian of the genome, is crucial for suppressing tumors. Emerging research suggests TP53 pathway genes also play a significant role in human fertility.
Area of Science:
- Molecular Biology
- Genetics
- Reproductive Biology
Background:
- The TP53 gene, identified in 1979 and recognized as a tumor suppressor in 1989, encodes the p53 protein, a critical regulator of cellular stress responses.
- The p53 protein acts as a transcription factor, inhibiting oncogenesis through apoptosis, senescence, and cell cycle arrest, and is frequently inactivated in cancers.
- While its role in cancer is well-established, recent findings indicate TP53's involvement in metabolism, autophagy, differentiation, development, and potentially fertility.
Purpose of the Study:
- To review the current understanding of TP53 family genes and the TP53 pathway concerning their functions in fertility.
- To present novel analyses of genomic and genotype databases to explore the TP53 pathway's role in human reproduction.
Main Methods:
- Literature review of TP53 family genes and the TP53 pathway in relation to fertility.
- Bioinformatic analysis of genomic and genotype databases.
Main Results:
- TP53 pathway genes are implicated in various cellular processes beyond tumor suppression.
- Genetic variations within the TP53 pathway suggest a role in human reproductive functions.
- Database analyses provide new insights into the TP53 pathway's involvement in reproduction.
Conclusions:
- The TP53 pathway's functions extend to regulating fertility, representing a new area of research.
- Further investigation into the TP53 pathway is warranted to fully understand its impact on human reproduction.
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