Research lead
Cancer Research UK-funded scientists at Dundee University and the Agency for Science Technology and Research in Singapore (A*STAR) have discovered how cells switch the tumour-suppressor gene p53a on and off. The discovery comes 30 years after p53 was discovered by David Lane, Cancer Research UK’s chief scientist. The finding has implications for cancer treatment and diagnosis.
The scientists found that the p53 gene makes not only the well-known p53 protein, but also an isoform. It is the isoform that feeds back to regulate the p53 gene. In its active state p53 triggers cell death (apoptosis) or arrests cell division to make repairs to DNA.
Scientists at Lane’s lab had previously discovered that cells contain more than one isoform of p53, but they did not know how the isoforms were produced, or what they did.
p53 is damaged or inactive in half of all cancers and also has roles in cell development and ageing. In normal cells it is activated in response to cell damage, triggering apoptosis when DNA is damaged beyond repair.
Lane said, “The function of p53 is critical to the way that many cancer treatments kill cells, since radiotherapy and chemotherapy act in part by triggering cell suicide in response to DNA damage. Understanding more about how this gene is controlled in cells is really important in finding ways to prevent cells from turning cancerous.”
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