University of Dundee

"Guardian of the Genome" Reveals More Secrets

25 Aug 2009

`Guardian of the Genome’ Reveals More Secrets

Scientists at the College of Life Sciences and the College of Medicine, Dentistry and Nursing at the University of Dundee have helped uncover new secrets regarding the function of a key gene – p53, known as the `Guardian of the Genome’, which is involved in around 90% of all cancers.

p53 was co-discovered by Professor Sir David Lane, of the College of Life Sciences at Dundee, 30 years ago. p53 is damaged or inactive in 90% of all cancers. In normal cells, it is activated in response to cell damage and one of its functions is to order cells either to repair the damage or to die - a process called apoptosis - when cells are damaged beyond repair. It is critical that p53 functions normally to prevent genetic mistakes being passed on to daughter cells which can lead to cancer. However, p53 activities to prevent cancer formation are complex; it is still difficult in many clinical studies to link p53 with cancer treatment.

Now Professor Lane and Doctor Jean-Christophe Bourdon, Principal Investigator in the Department of Surgery and Molecular Oncology at Dundee, – in collaboration with project leaders at the National Cancer Institute in Maryland, USA, and other partners in the USA, Czech Republic and Singapore - have made new breakthroughs which show how p53 can activate or suppress cell proliferation which controls ageing and tumour growth.

The research has been published online by the scientific journal Nature Cell Biology.

“In 2005, I discovered that p53 was not in fact just one gene encoding one protein but instead was producing eight different forms of p53 protein, also called p53 isoforms,” said Dr Bourdon.

“Now with our partners, we are starting to discover more about these eight p53 isoforms. In this latest research, we have found that two of the isoforms work like a brake and an accelerator, speeding up and slowing down p53 activity to control cell proliferation.

“An example of this would be sunburns. Our body works to kill off damaged cells and grow new healthy ones. If p53 is working normally then it will start and stop these processes at the right time. But if the balance between the p53 isoform activities is not correct then p53 is deregulated, the damaged cells are not killed and they can then proliferate, which can lead to tumour formation.”

It is hoped discoveries such as this will help identify biomarkers related to p53, which allow scientists to develop new drugs that could control the gene’s activity.

“What we are seeing now is the key steps which should eventually help us discover and develop drugs which would specifically target p53 and the processes it controls,” said Dr Bourdon.

The work is supported by Cancer Research UK, Breast Cancer Campaign and the French research institute Inserm.

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