Cancer Research UK scientists have discovered a missing link in the way cells protect themselves against cancer, according to research published in Genes & Development.
Cancer Research UK-funded scientists based at the The Univeristy of Dundee and the Agency for Science Technology and Research in Singapore (A*STAR) have discovered how cells switch p53, the tumour-suppressor gene known as the guardian of the genome, on and off. The discovery comes 30 years after it was co-discovered by Professor Sir David Lane, who is also Cancer Research UK's chief scientist. This has important implications for cancer treatment and diagnosis.
The scientists used a genetic trick to make zebrafish turn green when the p53 gene was switched on to explore the way this gene was regulated.
They found that the p53 gene makes not only the well-established p53 protein, but also an alternative 'control switch' variation of the p53 protein - known as an isoform. It is the isoform that feeds back to regulate the p53 gene. In its active state p53 will trigger cell death - called apoptosis - or arrest cell division to make repairs to DNA.
Normally zebrafish can survive low doses of radiation. But zebrafish which couldn't make this isoform 'switch', died when exposed to low levels of radiation. This proved that the isoform was critical in controlling p53â€s normal function to protect cells against the development of cancer - which includes ordering cells to die when they are badly damaged.
Scientists from Professor Sir David's lab had previously discovered that cells contained more than one isoform of p53 - but they didnâ€t know how the isoforms were produced or what they did.
Zebrafish carry the same p53 gene as humans.