Featured Research

from universities, journals, and other organizations

Study Reveals Cancer Role Of Mutated Gene

Date:
May 25, 1999
Source:
University Of North Carolina School Of Medicine
Summary:
Scientists at the University of North Carolina at Chapel Hill have discovered the molecular role in cancer development of a mutated tumor suppressor gene known as ARF. The new findings help clarify why ARF is the second most frequently mutated gene in human cancers, appearing in 40 percent of malignancies, second only to the mutated tumor suppressor gene, p53.

CHAPEL HILL, N.C. - Scientists at the University of North Carolina at Chapel Hill have discovered the molecular role in cancer development of a mutated tumor suppressor gene known as ARF.

Related Articles


The new findings help clarify why ARF is the second most frequently mutated gene in human cancers, appearing in 40 percent of malignancies, second only to the mutated tumor suppressor gene, p53.

According to a report in the journal Molecular Cell, published May 20, ARF normally prevents cellular transformation by preventing degradation of the p53 protein. It allows p53 to accumulate in the cell's nucleus where it functions to stop tumor cell growth.

"We previously reported our discovery that the ARF protein functions to suppress tumor growth by biochemically binding to another protein called MDM2," says Dr. Yue Xiong, assistant professor of biochemistry and biophysics at the UNC-CH School of Medicine. "Under normal conditions, MDM2 binds with p53 and takes it to the cellular cytoplasm for degradation. ARF will stop this process, accumulating p53 in the nucleus."

In the new study, Xiong and Dr.Yanping Zhang, a postdoctoral researcher in his laboratory at the UNC Lineberger Comprehensive Cancer Center, for the first time have described how a normally-functioning ARF does that. Essentially, it binds with MDM2 and p53 to form a structure called a nuclear body. This structure prevents MDM2 and p53 from leaving the nucleus and entering the cytoplasm, where the proteins would otherwise be degraded, broken down.

"When these proteins all come together, p53 cannot go from the nucleus to the cytoplasm. So ARF blocks p53 nuclear export," Xiong says.

The researchers also focused on what happens when ARF becomes mutated. They demonstrated for the first time how the ability of a mutated ARF to fulfill its tumor-suppressing role is impaired - a demonstration based on three discoveries.

First, Zhang and Xiong discovered that ARF is normally located in the cell's nucleolis, a small rounded mass within the cell's nucleus. Second, they determined the DNA sequence in ARF (located in an area of the gene called Exon 2) that is responsible for "localizing" or getting this protein directly to the nucleolis.

This finding led them to link ARF's Exon 2 with cancer, "because many ARF mutations associated with human cancer are clustered in this area and are predicted to disrupt ARF's normal localization," Xiong explains.

"So we tested whether mutations derived from cancer patients would mislocalize ARF and impair its ability to block p53 export and degradation. The answer is yes," Xiong states. "With ARF mutated and mislocalized, oncogenes go unchecked and cells proliferate abnormally, initiating oncogenesis."


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. "Study Reveals Cancer Role Of Mutated Gene." ScienceDaily. ScienceDaily, 25 May 1999. <www.sciencedaily.com/releases/1999/05/990525061736.htm>.
University Of North Carolina School Of Medicine. (1999, May 25). Study Reveals Cancer Role Of Mutated Gene. ScienceDaily. Retrieved November 23, 2014 from www.sciencedaily.com/releases/1999/05/990525061736.htm
University Of North Carolina School Of Medicine. "Study Reveals Cancer Role Of Mutated Gene." ScienceDaily. www.sciencedaily.com/releases/1999/05/990525061736.htm (accessed November 23, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, November 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com
Raw: Paralyzed Marine Walks With Robotic Braces

Raw: Paralyzed Marine Walks With Robotic Braces

AP (Nov. 21, 2014) Marine Corps officials say a special operations officer left paralyzed by a sniper's bullet in Afghanistan walked using robotic leg braces in a ceremony to award him a Bronze Star. (Nov. 21) Video provided by AP
Powered by NewsLook.com
Milestone Birthdays Can Bring Existential Crisis, Study Says

Milestone Birthdays Can Bring Existential Crisis, Study Says

Newsy (Nov. 21, 2014) Researchers find that as people approach new decades in their lives they make bigger life decisions. 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