The TP53 fertility network

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.

UBTD1 induces cellular senescence through an UBTD1-Mdm2/p53 positive feedback loop

“…Compared to its role in apoptosis, the role of p53 in cellular senescence is far from clear. As p53 is an important transcription factor and directly regulates numerous genes , it is unclear which of the p53 targets are part of the p53 downstream pathway that mediates induction of senescence. Hearnes et al identified >100 potential p53 downstream target genes using a chromatin immunoprecipitation (ChIP) assay, including known p53 targets as well as novel potential target genes, including UBTD1 .…”

Bridging the gap between genes and language deficits in schizophrenia: an oscillopathic approach

“…Notably, a binding site for MEF2A has been linked to formal thought disorder (Thygesen et al 2015). Likewise, TP53 exhibits a non-fixed change (P72R) compared to Neanderthals/Denisovans (Paskulin et al 2012) and the expression pattern of the human gene differs from the patterns observed in other primates (Konopka et al 2012). Risk alleles for TP53 seem to contribute to the reduced metabolic activity and the reduced white matter volumes observed in the frontal lobe of schizophrenics (Molina et al 2011).…”

The involvement of human endogenous retroviruses K (HERV-K) in aging processes via induction of inflammation

“…Additionally, both transcription factors compete for common cofactors (Wadgaonkar et al, 1999). Therefore, hyperactive NF-κB prote B reduces the tumor suppressor activity of p53 leading to oncogene-mediated transformation (Gudkov et al, 2011), because p53 contributes to the maintenance of the differentiated state and restrain dedifferentiation (Molchadsky et al, 2010;Paskulin et al, 2012). Lower p53 levels improve reprogramming efficiency of somatic cells into induced pluripotent stem cells (Kawamura et al, 2009).…”