Structure of protein vital to cancer development is mapped

A team from the UK comprised of members of The Institute of Cancer
Research, London, and the Medical Research Council Laboratory of
Molecular Biology, Cambridge, have produced the world's first detailed
images of the anaphase-promoting complex (APC/C).

Dr. David Barford, who has held positions at both institutions, led the study and says that the results are satisfying:

"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."

Integral to cell division

The APC/C is important as it is involved with a range of vital tasks
within the process of cell division, mitosis. During mitosis, a cell
duplicates itself, pulling apart its chromosomes into two separate
daughter cells. Mitosis occurs in animals and plants alike.

Thousands
of copies of cancer cells are created during cell division. New
research into the APC/C may eventually put a stop to this.

It is during cell division that cancer rears its ugly head, hijacking
the process in order to make hundreds of copies of harmful cancer cells.
By uncovering the full structure of a vital component of this process,
researchers may be able to discover new effective treatments for cancer.

Published in Nature and funded by the Cancer Research UK
charity, the research follows on from the team's previous work in which
they had been able to show a globular structure for the APC/C, but not
its important secondary structure - the set of building blocks that come
together to form every protein.

The researchers used a combination of electron microscopy and imaging
software to examine reconstituted human APC/C at a resolution of less
than a billionth of a meter, a far higher resolution than their previous
study.

This resolution was high enough that the researchers were able
to visualize the secondary structure. The overall architecture of the
APC/C was defined within its 20 subunits, where alpha-helix rods and
folded beta-sheet constructions were found by the researchers.

Interim Chief Executive of The Institute of Cancer Research Prof. Paul
Workman says that these insights illustrate the critical role that
fundamental cell biology plays in cancer research:

"The new study is a major step forward in our understanding of cell
division. When the 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."

Developing future treatments

Every subunit of the APC/C bonds and meshes with other units during
different points of the cell cycle. This bonding allows the APC/C to
control several mitotic processes, such as the initiation of DNA
copying, the separation of chromosomes and cytokinesis, the splitting of
one cell into two.

New cancer drugs that could be developed in light of this
research would target binding sites, disrupting these processes to
hopefully prevent cancer cells from dividing or even kill them
completely.

Dr. Kat Arney, Science Information Manager at Cancer Research UK, says
that "revealing the intricate details of biological shapes is a hugely
important step toward identifying targets for future cancer drugs." The
new research has certainly laid the APC/C bare, and this could prove to
be a vital milestone in the journey toward a cure for cancer.

Last week, Medical News Today reported on a study that discovered how cholesterol influences cancerous cell division.

Written by James McIntosh

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