SALT LAKE CITY Using advanced computer simulations, University of Utah College of Pharmacy researchers have produced moving images of a protein complex that is an important target for anti-cancer drugs. This advancement has significant implications for discovering new therapies that could attack cancer without damaging the DNA of healthy cells, according to an article published July 31, 2012 in the Proceedings of the National Academy of Sciences.
The researchers used high-performance computing technology to demonstrate that a protein complex called LSD1/CoREST undergoes major changes in shape, which are regulated by binding to a DNA-packaging protein known as histone H3. LSD1 gene expression is increased in many cancers and insight into the changes in the LSD1/CoREST complex may help to accelerate development of epigenetic drugs that reprogram cancer cells to behave more normally.
Epigenetics is the study of changes in gene expression that are not caused by alterations in the DNA itself. Instead, these changes are caused by chemical modifications that switch parts of the genome on and off to regulate gene activity. These chemical modifications occur within the epigenome, a layer of chemical labels that covers the genome, and help to determine whether specific genes are active or inactive. Epigenetic drug discovery is based on the knowledge that the epigenome is flexible and could potentially be altered by therapeutic drugs.
Lysine-specific demethylase-1 (LSD1)/CoREST is a protein complex involved in epigenetic changes. Recent studies have shown that LSD1-CoREST is a binding partner for various proteins involved in regulating genes and modifying chromatin, the combination of DNA and DNA-packaging proteins called histones that make up the nucleus of a cell. Previous research also revealed that LSD1-CoREST binds to histone H3.
"In our earlier work, we discovered that LSD1/CoREST functions as a tiny clamp that can reversi
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| Contact: Phil Sahm phil.sahm@hsc.utah.edu 801-581-2517 University of Utah Health Sciences Source:Eurekalert |
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