Featured Research

from universities, journals, and other organizations

X-ray protein probe leads to potential anticancer tactic

Date:
September 12, 2011
Source:
Emory University
Summary:
Researchers have identified a new type of potential anticancer drug. The compound, named FOBISIN, targets 14-3-3 proteins, important for the runaway growth of cancer cells. The researchers were using X-rays to see how FOBISIN fits into the clamp-shaped 14-3-3 protein structure. Unexpectedly, the X-rays induced the compound to be permanently bonded to the protein.

X-rays induce FOBISIN to become bonded to the 14-3-3 protein, suggesting a anticancer therapy tactic.
Credit: Image courtesy of Emory University

Researchers at Emory University School of Medicine have identified a new type of potential anticancer drug. The compound, named FOBISIN, targets 14-3-3 proteins, important for the runaway growth of cancer cells.

The researchers were using X-rays to see how FOBISIN fits into the clamp-shaped 14-3-3 protein structure. Unexpectedly, the X-rays induced the compound to be permanently bonded to the protein. The finding suggests that compounds like FOBISIN can be used in combination with radiation to trigger potent anticancer activity.

The results were published online Sept. 9 in Proceedings of the National Academy of Sciences Early Edition.

Senior author Haian Fu, PhD, has been studying 14-3-3 proteins for two decades. He is professor of pharmacology and of hematology and oncology at Emory University School of Medicine, and the director of the Emory Chemical Biology Discovery Center.

"Targeting 14-3-3 proteins could be especially valuable because they can impact multiple pathways critical for cancer cell growth," he says. "14-3-3 proteins have been shown to be dysregulated in a number of cancer types, including lung cancer and breast cancer."

14-3-3 proteins act as adaptors that clamp onto other proteins. Fu and co-workers Jing Zhao, postdoctoral fellow, and Yuhong Du, assistant professor and associate director of the Discovery Center, sorted through thousands of chemicals to find one (FOBISIN: Fourteen-three-three Binding Small molecule Inhibitor) that prevents 14-3-3 from interacting with its partners. 14-3-3 proteins are found in mammals, plants and fungi. In humans, they come in seven varieties, and FOBISIN appears to inhibit interactions by all seven.

A 14-3-3 proteins' ability to clamp depends on whether the target protein is phosphorylated, a chemical modification that regulates protein function. FOBISIN's inhibitory power also requires the presence of phosphorylation in the molecule.

Fu's group teamed up with the laboratory of Xiaodong Cheng, PhD, co-senior author, professor of biochemistry and a Georgia Research Alliance Eminent Scholar, to examine how FOBISIN fits into its targets.

Scientists use X-rays as a tool to probe protein structure. If a protein and a drug that targets it can be crystallized together, the X-ray diffraction pattern from the crystals reveals the 3D arrangement of the atoms and how the drug interacts with the protein. Research assistant professor John Horton, PhD, and research associate Anup Upadhyay, PhD, in the Cheng laboratory used synchrotron X-ray radiation from the Advanced Photon Source at Argonne National Laboratory for this purpose.

"In this case, the X-rays had an unexpected effect: they caused FOBISIN to become covalently attached to the 14-3-3 protein," Cheng says.

The finding suggests that compounds like FOBISIN could be developed as "pro-drugs" that upon exposure to radiation, permanently stick to and inhibit their targets. A common strategy in fighting cancer is to combine drugs and radiation so that the drugs increase cells' sensitivity to radiation. Here, the radiation would activate the drug.

"These compounds could be used in combination with other strategies to enhance the tumor selectivity of the treatment," Fu says.

The research was funded by the U.S. National Institutes of Health, the Georgia Cancer Coalition, and the Georgia Research Alliance.


Story Source:

The above story is based on materials provided by Emory University. The original article was written by Quinn Eastman. Note: Materials may be edited for content and length.


Journal Reference:

  1. J. Zhao, Y. Du, J. R. Horton, A. K. Upadhyay, B. Lou, Y. Bai, X. Zhang, L. Du, M. Li, B. Wang, L. Zhang, J. T. Barbieri, F. R. Khuri, X. Cheng, H. Fu. Discovery and structural characterization of a small molecule 14-3-3 protein-protein interaction inhibitor. Proceedings of the National Academy of Sciences, 2011; DOI: 10.1073/pnas.1100012108

Cite This Page:

Emory University. "X-ray protein probe leads to potential anticancer tactic." ScienceDaily. ScienceDaily, 12 September 2011. <www.sciencedaily.com/releases/2011/09/110912143557.htm>.
Emory University. (2011, September 12). X-ray protein probe leads to potential anticancer tactic. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2011/09/110912143557.htm
Emory University. "X-ray protein probe leads to potential anticancer tactic." ScienceDaily. www.sciencedaily.com/releases/2011/09/110912143557.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Microneedle Patch Promises Painless Pricks

Microneedle Patch Promises Painless Pricks

Reuters - Innovations Video Online (Oct. 18, 2014) Researchers at The National University of Singapore have invented a new microneedle patch that could offer a faster and less painful delivery of drugs such as insulin and painkillers. Video provided by Reuters
Powered by NewsLook.com
Raw: Nurse Nina Pham Arrives in Maryland

Raw: Nurse Nina Pham Arrives in Maryland

AP (Oct. 17, 2014) The first nurse to be diagnosed with Ebola at a Dallas hospital walked down the stairs of an executive jet into an ambulance at an airport in Frederick, Maryland, on Thursday. Pham will be treated at the National Institutes of Health. (Oct. 16) Video provided by AP
Powered by NewsLook.com
Raw: Cruise Ship Returns to US Over Ebola Fears

Raw: Cruise Ship Returns to US Over Ebola Fears

AP (Oct. 17, 2014) A Caribbean cruise ship carrying a Dallas health care worker who is being monitored for signs of the Ebola virus is heading back to Texas, US, after being refused permission to dock in Cozumel, Mexico. (Oct. 17) Video provided by AP
Powered by NewsLook.com
Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

AFP (Oct. 17, 2014) All four suspected Ebola cases admitted to hospitals in Spain on Thursday have tested negative for the deadly virus in a first round of tests, the government said Friday. Duration: 00:55 Video provided by AFP
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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