Fig. 6. Schematic model of TAp63 role in ovary physiology, in HET Δ13p63 mouse model and in presence of POI mutations.

Under normal physiological conditions, TAp63α is present in dimeric inactive form, which can be activated only upon certain circumstances such us upon DNA damage. Activated TAp63α enables DNA quality check to ensure the genomic stability of germline ovary development and follicle maturation. However, TAp63β, as well as POI mutants of p63, form active tetramers which constitutively induce cell death, leading to premature ovarian insufficiency.