Featured Research

from universities, journals, and other organizations

Crystal Structure Of Protein Interaction Could Lead To New Drugs Against Cancer

Date:
December 11, 2000
Source:
University Of North Carolina School Of Medicine
Summary:
Scientists at the University of North Carolina at Chapel Hill for the first time have identified the three dimensional crystal structure of two cellular proteins that when bound together play a key role in triggering the spread of cancer cells.

Chapel Hill - Scientists at the University of North Carolina at Chapel Hill for the first time have identified the three dimensional crystal structure of two cellular proteins that when bound together play a key role in triggering the spread of cancer cells.

The new findings are published in the December 7 issue of the international science journal Nature. They should help pave the way for deciphering exactly how this protein complex normally functions in the cell's molecular pathway and what can go wrong when either protein is mutated. Given this information, future drug discovery efforts can be aimed at targeting the interaction between specific proteins involved in making cancer cells invasive while causing little or no unwanted side effects.

In their research, scientist headed by John Sondek, PhD, assistant professor of pharmacology at UNC-CH School of Medicine focused on a specific family G proteins important in cellular growth control and architecture.

"You can think of a G protein as a light switch," Sondek said. "And there are many of these proteins in your body that are controlling numerous functions, depending on whether they're switched 'on' or 'off'."

The UNC researcher studies the Rho family of G proteins, which normally help regulate such important functions as cell shape, division, movement, proliferation - virtually every aspect of cellular change and development. In addition, Rho family G proteins are also implicated in malignant growth transformation.

According to Sondek, activation of these G proteins depends on the molecular signal they receive from other proteins called guanine nucleotide exchange factors or GEFs. "If GEFs are in their active form, they in turn activate the G protein. Trouble occurs when you get a perpetual 'on' state for these G-proteins, which can lead to malignancies."

Here, the 'on' position of the light switch occurs when the G protein is bound to the small molecule guanosine triphosphate or GTP. Through X-ray crystallography methods, which initially involve purification of the proteins, Sondek's team has determined the molecular structure of a Rho family G protein bound to its activator, the T-lymphoma and invasion metastasis factor, or Tiam1.

"This structure is essentially the G protein light switch half way between 'on' and 'off.' Now the question is, can we turn the light switch, or G protein, 'on' and 'off' at will?" asks Sondek.

A member of the UNC Lineberger Comprehensive Cancer Center and a Pew Biomedical scholar, Sondek has been studying Tiam1 because when it is over-expressed, it causes invasion and spreading of a lymphoma that is not normally invasive.

"Our work basically provides the details for understanding how these G proteins are activated," he said. "In terms of its clinical implications, Tiam1 is known for its ability to induce normally non-invasive T-lymphoma cancer cells to become invasive, and has subsequently been shown to produce experimental cancer metastasis in mice. A major difficulty in cancer treatment arises when cancer cells leave the site of the primary tumor and invade other parts of the body."

Moreover, notes the researcher, Tiam1 is present and in virtually all tumor cells analyzed. Sondek's long-term research will involve determining the structures of other G proteins and their activators to build up a set of data to which rational drug design can be applied. The structures will highlight points of protein interaction between the G proteins that may be targeted pharmacologically.

Co-authors of the Nature report are American Cancer Society fellow David Worthylake, PhD and Kent L. Rossman, a pre-doctoral fellow of the Lineberger Comprehensive Cancer Center and member of the biochemistry and biophysics department.


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.


Cite This Page:

University Of North Carolina School Of Medicine. "Crystal Structure Of Protein Interaction Could Lead To New Drugs Against Cancer." ScienceDaily. ScienceDaily, 11 December 2000. <www.sciencedaily.com/releases/2000/12/001211075431.htm>.
University Of North Carolina School Of Medicine. (2000, December 11). Crystal Structure Of Protein Interaction Could Lead To New Drugs Against Cancer. ScienceDaily. Retrieved October 1, 2014 from www.sciencedaily.com/releases/2000/12/001211075431.htm
University Of North Carolina School Of Medicine. "Crystal Structure Of Protein Interaction Could Lead To New Drugs Against Cancer." ScienceDaily. www.sciencedaily.com/releases/2000/12/001211075431.htm (accessed October 1, 2014).

Share This



More Health & Medicine News

Wednesday, October 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Some Positive Ebola News: Outbreak 'Contained' In Nigeria

Some Positive Ebola News: Outbreak 'Contained' In Nigeria

Newsy (Sep. 30, 2014) The CDC says a new case of Ebola has not been reported in Nigeria for more than 21 days, leading to hopes the outbreak might be nearing its end. Video provided by Newsy
Powered by NewsLook.com
UN Ebola Mission Head: Immediate Action Is Crucial

UN Ebola Mission Head: Immediate Action Is Crucial

AFP (Sep. 30, 2014) The newly appointed head of the United Nations Mission for Ebola Emergency Response (UNMEER), Anthony Banbury, outlines operations to tackle the virus. Duration: 00:39 Video provided by AFP
Powered by NewsLook.com
CDC Confirms First Case of Ebola in US

CDC Confirms First Case of Ebola in US

AP (Sep. 30, 2014) The CDC has confirmed the first diagnosed case of Ebola in the United States. The patient is being treated at a Dallas hospital after traveling earlier this month from Liberia. (Sept. 30) Video provided by AP
Powered by NewsLook.com
New Breast Cancer Drug Extends Lives In Clinical Trial

New Breast Cancer Drug Extends Lives In Clinical Trial

Newsy (Sep. 30, 2014) In a clinical trial, breast cancer patients lived an average of 15 months longer when they received new drug Perjeta along with Herceptin. 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:

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