Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Towards better anti-cancer drugs: New insights into CDK8, an important human oncogene


The Bayreuth biochemist Dr. Claus-D. Kuhn and his research team have deciphered how the important human oncogene CDK8 is activated in cells of healthy individuals. Their findings, which have now been published in the journal ‘Proceedings of the National Academy of Sciences U.S.A.’, explain why promising anti-CDK8 drugs are only effective under laboratory conditions but likely not in humans. Gained results also show a new way of developing CDK8-specific drugs in the future.

Most cancers are caused by a large variety of factors that vary from one person to another. To unravel this complexity, genes that contribute to the development of a respective cancer must be identified. Such genes are called oncogenes. A good example of an oncogene is CDK8: Cyclin-dependent kinase 8. Misregulated CDK8 is an important factor in the development of colon, breast and skin cancer.

Felix Klatt and Dr. Claus-D. Kuhn (r.) while working with High Five insect cells.

Photo: Juli Eberle

Felix Klatt utilizes an ÄKTA chromatography system to purify protein complexes that were instrumental to the publication.

Photo: Jürgen Rennecke

Hence, in recent years considerable efforts have been undertaken to develop drugs that specifically target CDK8 and that do not affect other molecules that are closely related to CDK8, but are essential for the survival of human cells.

A research team at the University of Bayreuth led by biochemist Dr. Claus-D. Kuhn has now discovered how CDK8 is activated in healthy humans. The research results are published in the journal ‘Proceedings of the National Academy of Sciences U.S.A.’. Apart from novel basic biochemical insights, the presented results suggest a new method by which CDK8-specific inhibitors could be developed in future.

MED12 binds and activates CDK8

The research team was mainly interested in how the oncogene CDK8 is activated in healthy cells. “One important aspect is that CDK8 does not occur in our cells as an individual molecule, but always in a complex with three partners. As part of this complex, CDK8 has completely different properties, which is why it is essential to investigate CDK8 as part of this complex”, explains the first author of the study, the Bayreuth graduate student Felix Klatt.

Using structural biochemistry – coupled with systems biology – the research team deciphered how CDK8 is activated by two of the three partners, Cyclin C and MED12. They demonstrated that just a tiny part of MED12 is responsible for activating CDK8. Due to its structure, the Bayreuth scientists named this part ‘MED12 activation helix’.

The ‘MED12 activation helix’ is often mutated in tumours

“After we discovered the ‘MED12 activation helix’, we were very surprised to find a large number of mutations associated with uterine fibroids, breast cancer and chronic lymphatic leukemia in this very area”, reports Dr. Claus-D. Kuhn, head of the Bayreuth research team ‘Gene Regulation by Non-coding RNA’, which is part of the Elite Network of Bavaria.

“To be honest, the extent of agreement between our basic biochemical research and the sequence analysis of human tumours was unexpected.”

Through subsequent biochemical experiments, his team was able to show that the mutations do not lead to a destabilization of the CDK8-containing complex, as previously suspected. Rather, there is a spatial rearrangement of the ‘MED12 activation helix’ within the complex, which leads to an abnormally reduced activity of CDK8 – a condition that most likely contributes to tumor development.

Hope for new CDK8-specific drugs

Binding of MED12 to CDK8 not only changes its activity, it also changes the active site of the enzyme CDK8. (By way of explanation: CDK8 is a so-called kinase, i.e. it modifies various target molecules with phosphate groups that are important for the cell’s gene reading machinery).

As Dr. Claus-D. Kuhn’s research group was able to show, this structural change leads to a situation in which so-called type II kinase inhibitors no longer bind effectively to CDK8 and inhibit it. “Conversely, this means that all future attempts to inhibit CDK8 must at least focus on triple complexes of CDK8, Cyclin C and MED12.

If, as has happened in the past, inhibitors are developed only against CDK8 in complex with Cyclin C, the resulting compounds are very likely ineffective against CDK8 in human cells”, concludes Dr. Claus-D. Kuhn.

Wissenschaftliche Ansprechpartner:

Dr. Claus-D. Kuhn
'Head of the Research group ‘Gene Regulation by Non-coding RNA’
Elite Network Bavaria and University of Bayreuth
Universitätsstraße 30 / NW I
Phone: +49 (0) 921 / 55-4356; mobile: +49 (0) 173 / 468 60 37


Felix Klatt et al.: A precisely positioned MED12 activation helix stimulates CDK8 kinase activity, Proc. Natl. Acad. Sci. U.S.A. (2020), DOI:

Christian Wißler | Universität Bayreuth

Further reports about: Cyclin MED12 anti-cancer anti-cancer drugs drugs human cells mutations oncogene tumours

More articles from Life Sciences:

nachricht Colorectal cancer: Increased life expectancy thanks to individualised therapies
20.02.2020 | Christian-Albrechts-Universität zu Kiel

nachricht Sweet beaks: What Galapagos finches and marine bacteria have in common
20.02.2020 | Max-Planck-Institut für Marine Mikrobiologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A step towards controlling spin-dependent petahertz electronics by material defects

The operational speed of semiconductors in various electronic and optoelectronic devices is limited to several gigahertz (a billion oscillations per second). This constrains the upper limit of the operational speed of computing. Now researchers from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and the Indian Institute of Technology in Bombay have explained how these processes can be sped up through the use of light waves and defected solid materials.

Light waves perform several hundred trillion oscillations per second. Hence, it is natural to envision employing light oscillations to drive the electronic...

Im Focus: Freiburg researcher investigate the origins of surface texture

Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.

Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...

Im Focus: Skyrmions like it hot: Spin structures are controllable even at high temperatures

Investigation of the temperature dependence of the skyrmion Hall effect reveals further insights into possible new data storage devices

The joint research project of Johannes Gutenberg University Mainz (JGU) and the Massachusetts Institute of Technology (MIT) that had previously demonstrated...

Im Focus: Making the internet more energy efficient through systemic optimization

Researchers at Chalmers University of Technology, Sweden, recently completed a 5-year research project looking at how to make fibre optic communications systems more energy efficient. Among their proposals are smart, error-correcting data chip circuits, which they refined to be 10 times less energy consumptive. The project has yielded several scientific articles, in publications including Nature Communications.

Streaming films and music, scrolling through social media, and using cloud-based storage services are everyday activities now.

Im Focus: New synthesis methods enhance 3D chemical space for drug discovery

After helping develop a new approach for organic synthesis -- carbon-hydrogen functionalization -- scientists at Emory University are now showing how this approach may apply to drug discovery. Nature Catalysis published their most recent work -- a streamlined process for making a three-dimensional scaffold of keen interest to the pharmaceutical industry.

"Our tools open up whole new chemical space for potential drug targets," says Huw Davies, Emory professor of organic chemistry and senior author of the paper.

All Focus news of the innovation-report >>>



Industry & Economy
Event News

70th Lindau Nobel Laureate Meeting: Around 70 Laureates set to meet with young scientists from approx. 100 countries

12.02.2020 | Event News

11th Advanced Battery Power Conference, March 24-25, 2020 in Münster/Germany

16.01.2020 | Event News

Laser Colloquium Hydrogen LKH2: fast and reliable fuel cell manufacturing

15.01.2020 | Event News

Latest News

Journey to the center of Mars

20.02.2020 | Physics and Astronomy

Laser writing enables practical flat optics and data storage in glass

20.02.2020 | Physics and Astronomy

New graphene-based metasurface capable of independent amplitude and phase control of light

20.02.2020 | Power and Electrical Engineering

Science & Research
Overview of more VideoLinks >>>