Featured Research

from universities, journals, and other organizations

New chemical probe provides tool to investigate role of malignant brain tumor domains in chromatin structure and regulation

Date:
March 1, 2013
Source:
University of North Carolina School of Medicine
Summary:
Medical researchers have discovered a chemical probe that can be used to investigate the L3MBTL3 methyl-lysine reader domain. The probe, named UNC1215, will provide researchers with a powerful tool to investigate the function of malignant brain tumor (MBT) domain proteins in biology and disease.

The chemical probe UNC1215 will be used to investigate the function of malignant brain tumor (MBT) domain protein, L3MBTL3, and study its role in different signaling pathways and disease.
Credit: Image courtesy of University of North Carolina School of Medicine

In an article published as the cover story of the March 2013 issue of Nature Chemical Biology, Lindsey James, PhD, research assistant professor in the lab of Stephen Frye, Fred Eshelman Distinguished Professor in the UNC School of Pharmacy and member of the UNC Lineberger Comprehensive Cancer Center, announced the discovery of a chemical probe that can be used to investigate the L3MBTL3 methyl-lysine reader domain. The probe, named UNC1215, will provide researchers with a powerful tool to investigate the function of malignant brain tumor (MBT) domain proteins in biology and disease.

"Before this there were no known chemical probes for the more than 200 domains in the human genome that recognize methyl lysine. In that regard, it is a first in class compound. The goal is to use the chemical probe to understand the biology of the proteins that it targets," said Dr. James.

Chromatin regulatory pathways play a fundamental role in gene expression and disease development, especially in the case of cancer. While many chemical probes work through the inhibition of enzyme activity, L3MBTL3 functions as a mediator of protein-to-protein interactions, which have been historically difficult to target with small, drug-like molecules.

"Many people believe that protein-protein interactions are difficult to target. Often they have a large surface area, so it is hard for small molecules to go in and intervene," said Dr. James.

Almost 40 percent of the genes that drive cancer can be mapped to dysfunction within signaling pathways. In the last five years, chemical probe development has allowed researchers to make fundamental observations of the role of these pathways in cancer development, as well as pointing to potential targets for new therapies. Each of the complex interactions within the signaling pathways represents a potential point where a therapy can be applied, and the probes allow researchers to interact with these processes at the molecular level and observe the overall effect of their perturbation on the disease state.

In a 2008 Nature Chemical Biology commentary, Dr. Frye outlined the qualities that make a good chemical probe. To Frye, a good chemical probe must be highly selective to enable specific questions to be asked and it must function as well in a cell as in the test tube, providing clear quantitative data with a well understood mechanism of action in either situation. It also must be available to all academic researchers without restrictions on its use, a criteria that the L3MBTL3 probe fulfills through the Frye lab's commitment to provide researchers with the probe free of charge on request and UNC1215 is already available through commercial vendors as well.

This research was supported by NIH grants (RC1GM090732 and R01GM100919) and the University Cancer Research Fund.


Story Source:

The above story is based on materials provided by University of North Carolina School of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Lindsey I James, Dalia Barsyte-Lovejoy, Nan Zhong, Liubov Krichevsky, Victoria K Korboukh, J Martin Herold, Christopher J MacNevin, Jacqueline L Norris, Cari A Sagum, Wolfram Tempel, Edyta Marcon, Hongbo Guo, Cen Gao, Xi-Ping Huang, Shili Duan, Andrew Emili, Jack F Greenblatt, Dmitri B Kireev, Jian Jin, William P Janzen, Peter J Brown, Mark T Bedford, Cheryl H Arrowsmith, Stephen V Frye. Discovery of a chemical probe for the L3MBTL3 methyllysine reader domain. Nature Chemical Biology, 2013; 9 (3): 184 DOI: 10.1038/nchembio.1157

Cite This Page:

University of North Carolina School of Medicine. "New chemical probe provides tool to investigate role of malignant brain tumor domains in chromatin structure and regulation." ScienceDaily. ScienceDaily, 1 March 2013. <www.sciencedaily.com/releases/2013/03/130301122308.htm>.
University of North Carolina School of Medicine. (2013, March 1). New chemical probe provides tool to investigate role of malignant brain tumor domains in chromatin structure and regulation. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/2013/03/130301122308.htm
University of North Carolina School of Medicine. "New chemical probe provides tool to investigate role of malignant brain tumor domains in chromatin structure and regulation." ScienceDaily. www.sciencedaily.com/releases/2013/03/130301122308.htm (accessed July 28, 2014).

Share This




More Health & Medicine News

Monday, July 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Trees Could Save More Than 850 Lives Each Year

Trees Could Save More Than 850 Lives Each Year

Newsy (July 27, 2014) A national study conducted by the USDA Forest Service found that trees collectively save more than 850 lives on an annual basis. Video provided by Newsy
Powered by NewsLook.com
Google's Next Frontier: The Human Body

Google's Next Frontier: The Human Body

Newsy (July 27, 2014) Google is collecting genetic and molecular information to paint a picture of the perfectly healthy human. Video provided by Newsy
Powered by NewsLook.com
What's To Blame For Worst Ebola Outbreak In History?

What's To Blame For Worst Ebola Outbreak In History?

Newsy (July 27, 2014) A U.S. doctor has tested positive for the deadly Ebola virus, as the worst-ever outbreak continues to grow. Video provided by Newsy
Powered by NewsLook.com
Losing Sleep Leaves You Vulnerable To 'False Memories'

Losing Sleep Leaves You Vulnerable To 'False Memories'

Newsy (July 27, 2014) A new study shows sleep deprivation can make it harder for people to remember specific details of an event. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins