Maeso-Alonso Laura, López-Ferreras Lorena, Marques Margarita M, Marin Maria C
Departamento de Biología Molecular, Instituto de Biomedicina (IBIOMED), University of León, León, Spain.
Departamento de Producción Animal, Instituto de Desarrollo Ganadero y Sanidad Animal, University of León, León, Spain.
Front Cell Dev Biol. 2021 Jul 23;9:716957. doi: 10.3389/fcell.2021.716957. eCollection 2021.
The 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 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 phenotypes.
该基因属于由p53、p63和p73组成的p53家族。响应生理和病理信号时,这些转录因子调控多个分子途径,这些途径汇聚于相互连接的网络整体中,其中细胞增殖和细胞死亡的控制占据突出地位。然而,该基因缺陷小鼠的复杂表型表明,该基因的生物学相关性并非仅依赖于其生长抑制作用,还与调控组织生理学不同方面的其他基本作用相互交织。p73的功能对于不同复杂微环境的组织和稳态至关重要,如支持神经祖细胞和室管膜的神经发生微环境、雄性和雌性生殖器官、呼吸道上皮或血管网络。我们提出,所有这些明显不相关的发育作用有一个共同特征:p73作为组织构建者发挥作用。组织结构由其细胞和细胞外区室的性质和完整性定义,它基于适当的细胞间和细胞与细胞外基质的粘附相互作用以及细胞极性的建立。在这项工作中,我们将通过对细胞粘附(细胞黏附)、细胞骨架动力学和平面细胞极性的调控来综述当前对p73作为神经发生微环境构建者作用的理解,并对TAp73作为这些功能的枢纽调节因子进行概述,其改变可能影响许多相关表型。 (注:括号内“细胞黏附”为补充完整“细胞间和细胞与细胞外基质的粘附”表述,使意思更清晰,按要求未添加其他解释说明,但实际翻译时可根据情况灵活处理使译文更通顺自然)