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.
Highlights
The transcription factor p53 is encoded by the Tumor Protein p53 gene (TP53, OMIM 191170), which in humans is located on the short arm of chromosome 17 (17p13.1)
TP53 is composed of 19,198 nucleotides, spanning 11 exons and encoding a 393 amino acid protein that functions primarily as a transcription factor and is biologically active as a homotetramer
DNp63 isoforms play distinct roles in regulating epithelium-mesenchyme interactions through the regulation of TGFb, resulting in a more invasive phenotype in the presence of DNp63g (Lindsay et al, 2011; Oh et al, 2011). p73 is involved in the development of the immune and central nervous system (Belyi et al, 2010) and has important functions in the regulation of the spindle assembly checkpoint (SAC) during meiosis and mitosis (Tomasini et al, 2008), as it prevents aneuploidy through sensing the improper attachment of sister chromatids to the mitotic or meiotic spindle and delays anaphase until chromosomes are correctly oriented for segregation (Gardner and Burke, 2000)
Summary
The transcription factor p53 is encoded by the Tumor Protein p53 gene (TP53, OMIM 191170), which in humans is located on the short arm of chromosome 17 (17p13.1). (2007b) demonstrated that p53 plays a significant role in fertility, since p53-null female mice present reduced uterine expression of LIF and, as expected, reduced maternal reproduction due to impaired implantation functions.
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