Tissue-specific expression of p73 C-terminal isoforms in mice

Abstract

p73 is a p53 family transcription factor. Due to the presence in the 5′ flanking region of two promoters, there are two N-terminal variants, TAp73, which retains a fully active transactivation domain (TA), and ΔNp73, in which the N terminus is truncated. In addition, extensive 3′ splicing gives rise to at least seven distinctive isoforms; TAp73-selective knockout highlights its role as a regulator of cell death, senescence and tumor suppressor. ΔNp73-selective knockout, on the other hand, highlights anti-apoptotic function of ΔNp73 and its involvement in DNA damage response. In this work, we investigated the expression pattern of murine p73 C-terminal isoforms. By using a RT-PCR approach, we were able to detect mRNAs of all the C-terminal isoforms described in humans. We characterized their in vivo expression profile in mouse organs and in different mouse developmental stages. Finally, we investigated p73 C-terminal expression profile following DNA damage, ex vivo after primary cultures treatment and in vivo after systemic administration of cytotoxic compounds. Overall, our study first elucidates spatio-temporal expression of mouse p73 isoforms and provides novel insights on their expression-switch under triggered conditions.

p73 Regulates Primary Cortical Neuron Metabolism: a Global Metabolic Profile

“…Notwithstanding these differences, mice generated by genetic deletion of the whole tp73 gene (p73-/-) [22] or selective N-terminal isoforms (TAp73-/-and Np73-/-) [23,24] all show postnatal alterations affecting the central nervous system (CNS). Indeed, the hippocampal dysgenesis observed in p73-/-and TAp73-/-mice manifests around 6 days of age, in agreement with the reported increase in TAp73 expression during neuronal maturation [25,26]. On the other hand, the neuronal loss and reduced cognitive and motor functions affecting ΔNp73-/-mice starts to be significantly evident in aged (26-27 months old) mice [24].…”

GLS2 is transcriptionally regulated by p73 and contributes to neuronal differentiation

“…[11][12][13][14][15] It is involved in several biological processes, such as cell death, [16][17][18][19] differentiation, [20][21][22] neuronal stem cell maintenance, [23][24][25][26] the amino acid Glutamine is converted into Glutamate by a deamidation reaction catalyzed by the enzyme Glutaminase (GLS). two isoforms of this enzyme have been described, and the GLS2 isoform is regulated by the tumor suppressor gene p53.…”

Molecular dynamics of the full-length p53 monomer

“…Both in cancer progression, metastasis, and in physiological development, all members of the family interact and regulate each other. 117,118 This is, for example, evident in epidermis, 119 as well as in DNA damage response. 120 The p53 protein is highly conserved in its structure from C. elegans, D. melanogaster to H. sapiens.…”