Abstract
The TP73 gene belongs to the p53 family comprised by p53, p63, and p73. In response to physiological and pathological signals these transcription factors regulate multiple molecular pathways which merge in an ensemble of interconnected networks, in which the control of cell proliferation and cell death occupies a prominent position. However, the complex phenotype of the Trp73 deficient mice has revealed that the biological relevance of this gene does not exclusively rely on its growth suppression effects, but it is also intertwined with other fundamental roles governing different aspects of tissue physiology. p73 function is essential for the organization and homeostasis of different complex microenvironments, like the neurogenic niche, which supports the neural progenitor cells and the ependyma, the male and female reproductive organs, the respiratory epithelium or the vascular network. We propose that all these, apparently unrelated, developmental roles, have a common denominator: p73 function as a tissue architect. Tissue architecture is defined by the nature and the integrity of its cellular and extracellular compartments, and it is based on proper adhesive cell-cell and cell-extracellular matrix interactions as well as the establishment of cellular polarity. In this work, we will review the current understanding of p73 role as a neurogenic niche architect through the regulation of cell adhesion, cytoskeleton dynamics and Planar Cell Polarity, and give a general overview of TAp73 as a hub modulator of these functions, whose alteration could impinge in many of the Trp73–/– phenotypes.
Highlights
The TP73 gene belongs to an evolutionary conserved family of transcription factors, the p53 family, with key functions to vertebrate’s biology
It is worth noting that the molecular networks involved in cell-tocell adhesion revealed by Santos Guasch et al (2018) in a total Trp73 knockout scenario are further supported by the recent study of López-Ferreras et al (2021), with specific inactivation of TAp73 in mouse embryonic stem cells (mESCs), emphasizing the interest of this fine-tuned cellular model to decipher the role of the Trp73 gene isoforms
Since its serendipitous discovery (Kaghad et al, 1997), p73 tumor suppression function was expected by virtue of its homology with p53 and its localization to chromosome 1p36, a region that is frequently deleted in a variety of tumors (Ichimiya et al, 1999)
Summary
The TP73 gene belongs to an evolutionary conserved family of transcription factors, the p53 family, with key functions to vertebrate’s biology. Like the regulation of cell adhesion establishment, cytoskeleton dynamics, multiciliogenesis and Planar Cell Polarity (PCP) are related to the maintenance of the structural organization and homeostasis of different complex microenvironments, like the neurogenic niche and the ependymal barrier in the central nervous system (CNS), the respiratory and reproductive epithelia, or the vascular network.
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