Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

U. of Colorado researchers solve molecular structure involved with heart disease

17.04.2003


A group of researchers led by the University of Colorado at Boulder have solved the crystal structure of a molecule switch that can trigger heart disease and cancer, paving the way for future drug designs to mitigate these diseases.



The key component of the switch is a protein called MEF2 that binds to the DNA and is involved in muscle cell, T cell and nerve cell development. In cases involving human hearts, it can lower gene activity that causes enlarged hearts, known as hypertrophic cardiomyopathy, said Assistant Professor Lin Chen of CU-Boulder’s chemistry and biochemistry department who is leading the study.

MEF2 works in part by recruiting proteins known as histone deacetylases, or HDACs, that can modify DNA structure to suppress specific gene expression. MEF2 does so by either binding directly to HDACs or to an adaptor protein known as Cabin1 that in turn binds to HDACs.


Chen and his team recently determined the crystal structure of MEF2 that is bound to the molecule Cabin1 on DNA. Their studies revealed for the first time the detailed mechanisms by which MEF2 suppresses genes inside cells.

"The structure not only showed us how genes are properly silenced into a quiescent state by MEF2 and its associated molecules," said Chen, "but more importantly, it also suggested potential mechanisms by which MEF2 activates gene expression when cells are stimulated, especially when cells are inappropriately activated during hypertrophic responses in one’s heart."

A paper on the subject will be published in the April 17 issue of Nature. The first author is Aidong Han, a postdoctoral fellow in the Chen lab. Other authors include James Stroud, a CU graduate student in the Chen lab, and Fan Pan, Hong-Duk Youn and Jun O. Liu from Johns Hopkins University in Baltimore.

MEF2 and HDACs have drawn much attention because of their medical relevance, playing a key role in heart hypertrophy, which is often a response to other heart diseases and eventually turns into heart failure, said Chen. In the Western World, cardiovascular diseases account for about 43 percent of human deaths and for about 50 percent of all human hospitalizations.

The function of HDACs also is the focus of intensive medical research, said Chen. Scientists have shown that inhibitors of HDACs can halt the proliferation of tumor cells and cause them to die.

A number of HDAC inhibitors now are in clinical trials as anti-cancer drugs, he said, and there are continued efforts to search for more specific and less toxic blockers of HDACs. "The picture we have now by which HDACs are recruited to DNA will undoubtedly help this endeavor," he said.

"The structure reported by our lab is exciting because it suggests potential strategies for development of drugs to block the activity of HDACs and prevent MEF2 from activating genes in diseased cells," said Chen. "These drugs may help patients with heart disease and hopefully some cancers, benefiting human health enormously."


Contact:

Lin Chen, 303-735-0071, Lin.Chen@colorado.edu
Aidong Han, 303-492-2503, hanna@colorado.edu
Jim Scott, 303-492-3114

Lin Chen | EurekAlert!
Further information:
http://www.colorado.edu/

More articles from Life Sciences:

nachricht Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo

nachricht Research reveals how order first appears in liquid crystals
23.05.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Space-like gravity weakens biochemical signals in muscle formation

23.05.2018 | Life Sciences

NIST puts the optical microscope under the microscope to achieve atomic accuracy

23.05.2018 | Physics and Astronomy

Magnesium magnificent for plasmonic applications

23.05.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>