p63 – the cause of female infertility

Cancer treatment can often leave women infertile and researchers in Germany believe they have begun to unveil the mechanism just why this happens

Oocytes exposed to radiation are destroyed by p63

Quality control in oocytes is different male germ cells – male germ cells are generated throughout the whole life span, but the number of female germ cells is fixed before birth. If damaged during cancer treatments, oocytes are destroyed by the female quality control system.

Professor Volker Dötsch from the Institute of Biophysical Chemistry at Goethe University and his international partners have discovered that the protein p63 is essential in oocyte destruction.  

The level of p63 in normal oocytes is high, and the protein is kept in a closed dimeric and inactive state, but when DNA is exposed to radioactive radiation, p63 can become phosphorylated. As a result, p63 changes to an open state, allowing the attachment of a second phosphorylated dimer. The p63 initiates programmed cell death, and the oocyte is destroyed.

p63 also shows an additional function: it is essential for the maintenance of stem cells in epithelial layers like skin, a function that shows the evolutionary process of a closely related protein family – p53 – from p63-like proteins.

Often named as the ‘guardian of the genome’, p53 is involved in the regulation of cell division and cell death of damaged cells. It therefore plays a key role in the suppression of genetic anomalies that could lead to cancer and p53 is altered in more than half of human tumours.

Its functioning is similar to that of p63 – if anomalies occur, the concentration increases and four p53 proteins form a tetramer. In this state, the tumour suppressor is active and initiates repair of damaged DNA or apoptosis.