posted on 2016-02-26, 10:29authored byIvano Amelio, Francesca Grespi, M. Annicchiarico-Petruzzelli, Gerry Melino
p63 is a transcriptional factor implicated in cancer and development. The presence in TP63 gene of alternative promoters allows expression of one isoform containing the N-terminal transactivation domain (TA isoform) and one N-terminal truncated isoform (ΔN isoform). Complete ablation of all p63 isoforms produced mice with fatal developmental abnormalities, including lack of epidermal barrier, limbs and other epidermal appendages. Specific TAp63-null mice, although they developed normally, failed to undergo in DNA damage-induced apoptosis during primordial follicle meiotic arrest, suggesting a p63 involvement in maternal reproduction. Recent findings have elucidated the role in DNA damage response of a novel Hominidae p63 isoform, GTAp63, specifically expressed in human spermatic precursors. Thus, these findings suggest a unique strategy of p63 gene, to evolve in order to preserve the species as a guardian of reproduction. Elucidation of the biological basis of p63 function in reproduction may provide novel approaches to the control of human fertility.
Funding
This work has been supported by the Medical Research Council,
United Kingdom; MIUR, MinSan, RF73, RF57, ACC12;
Odysseus Grant (G.0017.12) from the Flemish government and
Flanders Institute for Biotechnology, Belgium.