Chemical probe to dissect role of potential cancer-causing proteins

October 26, 2015, Institute of Cancer Research
Electron microscopic image of a single human lymphocyte. Credit: Dr. Triche National Cancer Institute

Scientists have created a highly specific and well-characterised chemical probe which can switch off two important proteins implicated in cancer—shedding new light on the role these proteins play in driving cancer cell proliferation.

A major new study, published in Nature Chemical Biology today (Monday), announces the discovery of the first highly selective modulator of two proteins called CDK8 and CDK19—members of an important family known as kinases—whose function is to regulate gene activation.

This well-characterised will allow more precise analysis than ever before of the biological the roles of CDK8 and CDK19 in and other cells.

The study comes from a research partnership between The Institute of Cancer Research, London, the University of Cardiff, pharmaceutical company Merck Serono, and Cancer Research Technology—the commercial arm of Cancer Research UK, which was one of the study's funders.

The chemical probe (CCT251545) - published by the same team earlier this year—was discovered by screening a large collection of chemicals against the WNT signalling pathway in cancer cells.

In the new study, the team describe the discovery that CDK8 and CDK19 are the biochemical targets of CCT251545.

The researchers report their work using a range of biological and biophysical techniques to show that CCT251545 potently and selectively binds to CDK8 and CDK19. They go on to explain how the probe binds to CDK8 and CDK19 and how this in turn blocks the WNT signalling pathway, a known driver of many bowel cancers.

Study co-leader Professor Julian Blagg, Deputy Director of the Cancer Research UK Cancer Therapeutics Unit at The Institute of Cancer Research, London, said:

"This collaborative study describes our detailed characterisation of CCT251545 as a highly specific chemical probe for the kinases CDK8 and CDK19 that control gene activation. Publishing our work will enable the scientific community to use our probes to further explore the role of these closely related proteins in cancer and other diseases."

Study co-leader Professor Trevor Dale, Deputy Head of Molecular Biosciences at Cardiff University, said:

"This study is a superb example of how an inter-disciplinary team of scientists from academia and industry can cooperate to produce work of the highest quality. It is great to look back and see how much was achieved."

Fellow study author Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

"The discovery of this new, highly specific chemical probe could help us to shed new light on an important pathway in cancer—and in biology generally—and help researchers to understand how to influence and exploit it.

"Chemical probes are very important tools in the development of new drugs, because they allow us to explore the effect of blocking cancer-causing proteins in cells. Our discovery through collaborative team science of highly potent, selective inhibitors for cancer proteins addresses an important need to find such probes for the huge area of the cancer signalling network that is still largely unexplored."

Explore further: Study shows molecule isolated from sea sponges may be effective treatment against leukemia

More information: A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease, Nature Chemical Biology, DOI: 10.1038/nchembio.1952

Related Stories

Study shows molecule isolated from sea sponges may be effective treatment against leukemia

September 28, 2015
A team of Harvard researchers and other collaborators led by Professor of Chemistry and Chemical Biology Matthew Shair has demonstrated that a molecule isolated from sea sponges and later synthesized in Shair's lab, can halt ...

A new approach to improving cancer chemotherapy

August 7, 2012
(Medical Xpress) -- Chemotherapy kills tumor cells, but it also wreaks havoc on the rest of the body. A team of researchers led by Igor Roninson of the South Carolina College of Pharmacy just reported the discovery of a new ...

Clearing a path for cancer research

September 10, 2015
EMBL-EBI researchers have developed a new computational method to study biological signalling networks in healthy and cancer cells.

Protein linked with tumor growth could be potential target for cancer-fighting drugs

June 6, 2013
As tumors grow, their centers are squeezed of oxygen. And so tumors must flip specific genetic switches to survive in these hypoxic environments. A series of studies funded to do only basic science and published today in ...

Recommended for you

Scientists discover chemical which can kill glioblastoma cells

August 15, 2018
Aggressive brain tumour cells taken from patients self-destructed after being exposed to a chemical in laboratory tests, researchers have shown.

Three scientists share $500,000 prize for work on cancer therapy

August 15, 2018
Tumors once considered untreatable have disappeared and people previously given months to live are surviving for decades thanks to new therapies emerging from the work of three scientists chosen to receive a $500,000 medical ...

PARP inhibitor improves progression-free survival in patients with advanced breast cancers

August 15, 2018
In a randomized, Phase III trial led by researchers at The University of Texas MD Anderson Cancer Center, the PARP inhibitor talazoparib extended progression-free survival (PFS) and improved quality-of-life measures over ...

New clues into how 'trash bag of the cell' traps and seals off waste

August 15, 2018
The mechanics behind how an important process within the cell traps material before recycling it has puzzled scientists for years. But Penn State researchers have gained new insight into how this process seals off waste, ...

RUNX proteins act as regulators in DNA repair, study finds

August 15, 2018
A study by researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore has revealed that RUNX proteins are integral to efficient DNA repair via the Fanconi Anemia (FA) ...

Chemicals found in vegetables prevent colon cancer in mice

August 14, 2018
Chemicals produced by vegetables such as kale, cabbage and broccoli could help to maintain a healthy gut and prevent colon cancer, a new study from the Francis Crick Institute shows.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.