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Mapping of cell division protein may aid cancer fight

A doorway to new cancer treatments has been opened by UK scientists who have mapped the structure of one of nature’s most important proteins.

Detailed images of the molecule and the building blocks from which it is composed are expected to shed new light on the mechanics of cell division.

They could also reveal previously unknown targets for future cancer drugs.

“Revealing the intricate details of biological shapes is a hugely important step towards identifying targets for future cancer drugs”

Kat Arney

The anaphase-promoting complex (APC/C) performs a wide range of vital tasks linked to mitosis, the process by which chromosomes are copied and shared when a cell divides into two.

Mitosis is fundamental to cell division in all animals and plants. Understanding the structure of APC/C could also open up a new front in the fight against cancer, which hijacks the normal process of cell division.

Professor David Barford, who led the team from the Institute of Cancer Research (ICR), London, said: “It’s very rewarding to finally tie down the detailed structure of this important protein, which is both one of the most important and most complicated found in all of nature.

“We hope our discovery will open up whole new avenues of research that increase our understanding of the process of mitosis, and ultimately lead to the discovery of new cancer drugs,” he said.

ICR

David Barfield

The scientists used a combination of electron microscopy and imaging software to visualise the protein at a resolution of less than a nanometre, or a millionth of a millimetre.

That is roughly equivalent to between three and six atoms placed side-by-side. A human hair is about 60,000 nanometres thick.

With this kind of detail, basic building blocks within the 20 subunits of the molecule were clearly visible.

Each of the subunits bond and mesh with other units at different points in the cell cycle, the series of events that leads to a cell splitting in two.

Disrupting one or more of these binding processes could selectively prevent cancer cells dividing and halt progression of the disease.

The results have been published in the online edition of the journal Nature.

Commenting on the study, ICR interim chief executive Professor Paul Workman said: “The fantastic insights into molecular structure provided by this study are a vivid illustration of the critical role played by fundamental cell biology in cancer research.

ICR

Paul Workman

“The new study is a major step forward in our understanding of cell division. When this process goes awry it is a critical difference that separates cancer cells from their healthy counterparts.

“Understanding exactly how cancer cells divide inappropriately is crucial to the discovery of innovative cancer treatments to improve outcomes for cancer patients.”

Dr Kat Arney, science information manager at Cancer Research UK, which funded the study, said: “Figuring out how the fundamental molecular ‘nuts and bolts’ of cells work is vital if we’re to make progress understanding what goes wrong in cancer cells and how to tackle them more effectively.

“Revealing the intricate details of biological shapes is a hugely important step towards identifying targets for future cancer drugs,” she said.

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