'Jekyll-and-Hyde' nature of molecule finally explained

In collaboration with the Press Association

The 'Jekyll-and-Hyde' behaviour of a molecule involved in cancer has been explained in a study part-funded by Cancer Research UK.

The study involved a comprehensive biological analysis of the molecule E2F, which is abnormal in many cancers.

Subtle changes in the protein's chemistry were found to have dramatic and opposite effects on the tumour cells, either allowing them to continuously grow, or else switching to death mode and destroying the cells.

The findings provide a fresh approach to developing new types of cancer drugs.

"We are excited by this new discovery," said Professor Nick La Thangue of the Department of Oncology at Oxford University.

"This mechanism for switching a key protein is very novel. Nothing else I've come across behaves like it."

Cells in the body go through cycles of growth and division, pauses and death in a highly regulated way. Cancer involves the breakdown of these controls leading to unlimited expansion of the cells in a growing tumour.

The protein E2F is inextricably linked to cancer. While it can be a factor driving the disease, it can also offer protection by removing damaged cells.

It is this dual Jekyll-and-Hyde nature of E2F that the researchers have been able to explain for the first time

The researchers showed that two enzymes compete to attach a molecular 'flag' on different parts of the E2F protein. The flag in one position is linked to E2F causing cell death and the same flag in another position is linked to E2F boosting cell growth and proliferation.

They have since found compounds in the laboratory that can block E2F's growth mode in cancer cells and reinstate it's cell-killing mode.

Dr Kat Arney, science information manager at Cancer Research UK, said: "Cancer is a complex biological problem, and getting to grips with the molecules that drive it is essential if we're to find new cures.

"Although there's a lot more work to be done before this new discovery could become a treatment for patients, this research is an important step forward in understanding E2F's 'split personality' in both driving and destroying cancer cells."

The research, which is published in the journal Molecular Cell, was led by a team from Oxford University, with collaborators in Singapore and the USA. It was funded by the UK Medical Research Council and Cancer Research UK.

Copyright Press Association 2013

References

Zheng S. et al. (2013). Arginine Methylation-Dependent Reader-Writer Interplay Governs Growth Control by E2F-1 Molecular Cell, DOI: