Featured Research

from universities, journals, and other organizations

Protein 'motif' crucial to telomerase activity

Date:
September 19, 2013
Source:
The Wistar Institute
Summary:
In an effort to understand and control telomerase activity, researchers have discovered a protein "motif," named TFLY, which is crucial to the function of telomerase. Altering this motif disrupts telomerase function, they found, a fact that they believe will help them in their efforts to identify inhibitors of telomerase with potential cancer therapeutic properties.

This model structure of the catalytic portion of telomerase shows how the TFLY motif (green) is positioned at the entry of the pocket that guides the RNA template in the interior cavity of the telomerase ring and were the active site of the enzyme if located for catalysis.
Credit: Emmanuel Skordalakes/The Wistar Institute

It is difficult to underestimate the importance of telomerase, an enzyme that is the hallmark of both aging and the uncontrolled cell division associated with cancer. In an effort to understand and control telomerase activity, researchers at The Wistar Institute have discovered a protein "motif," named TFLY, which is crucial to the function of telomerase. Altering this motif disrupts telomerase function, they found, a fact that they believe will help them in their efforts to identify inhibitors of telomerase with potential cancer therapeutic properties.

Their findings are published in the October 8 issue of the journal Structure, available online now.

"Telomerase is a unique protein-RNA complex where the protein subunit uses its RNA component as a template to add identical fragments of DNA to the end of chromosomes," said Emmanuel Skordalakes, Ph.D., associate professor in the Gene Expression and Regulation program of Wistar's NCI-designated Cancer Center. "We identified a motif in the protein component of telomerase that controls how the enzyme carries out its activity in vertebrates such as ourselves."

"If you disrupt this segment of the protein, by altering its amino acid sequence, you disrupt the ability of telomerase to function," Skordalakes explained. "Obviously, this information can be used in our efforts to identify drug therapies that kill cancer cells by targeting telomerase activity."

Telomerase is an enzyme that replicates the ends of chromosomes (sections of DNA called telomeres), replacing the DNA lost when chromosomes are copied before cell division and, therefore, maintaining the stability of the genome. It performs this critical service in embryonic development, growing organisms and in a few specialized adult cell lines, including stem cells.

In most normal adult cells, however, telomerase is switched off almost entirely to prevent the dangers of runaway cell proliferation. Without telomerase, adult cells senesce (grow old) after about 50-55 rounds of cell division because the telomeres get too short to provide the buffer required to protect the ends of chromosomes and stabilize the cell's genetic code.

It is now established that nearly 90 percent of cancers develop a way of reactivating telomerase as a means of survival. Inhibiting telomerase function has been viewed as an ideal way to put the brakes on a wide range of cancers. According to Skordalakes, one way to do so would be to disrupt the protein RNA complex that comprises the core of the telomerase enzyme. The RNA binding domain (TRBD) of telomerase is a crucial component to this process and, therefore, the enzyme's ability to work.

In 2007, the Skordalakes laboratory was the first to obtain the three-dimensional structure of TRBD. Since then, his team has been creating molecular inhibitors to target the TRBD RNA-binding pockets as means to inhibit telomerase enzymatic activity.

The present study arose as the Skordalakes laboratory sought to better understand the role of TRBD in telomerase function. They engineered a truncated version of the protein subunit of a vertebrate telomerase, consisting of TRBD and a conserved portion of the N-terminal region of the protein. Within this portion they identified the TFLY, a conserved element that they showed is involved in binding the RNA component of telomerase and this interaction is important for telomerase protein-RNA assembly and activity.

"This TFLY motif comprises a significant part of the binding pocket that enables the enzyme to grapple the RNA template and guide it to the active site of the enzyme for catalysis," Skordalakes said, "but it also facilitates the stable association of the protein with its RNA component thus forming a fully functional telomerase enzyme."


Story Source:

The above story is based on materials provided by The Wistar Institute. Note: Materials may be edited for content and length.


Cite This Page:

The Wistar Institute. "Protein 'motif' crucial to telomerase activity." ScienceDaily. ScienceDaily, 19 September 2013. <www.sciencedaily.com/releases/2013/09/130919122304.htm>.
The Wistar Institute. (2013, September 19). Protein 'motif' crucial to telomerase activity. ScienceDaily. Retrieved April 19, 2014 from www.sciencedaily.com/releases/2013/09/130919122304.htm
The Wistar Institute. "Protein 'motif' crucial to telomerase activity." ScienceDaily. www.sciencedaily.com/releases/2013/09/130919122304.htm (accessed April 19, 2014).

Share This



More Health & Medicine News

Saturday, April 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

'Holy Grail' Of Weight Loss? New Find Could Be It

'Holy Grail' Of Weight Loss? New Find Could Be It

Newsy (Apr. 18, 2014) In a potential breakthrough for future obesity treatments, scientists have used MRI scans to pinpoint brown fat in a living adult for the first time. Video provided by Newsy
Powered by NewsLook.com
Little Progress Made In Fighting Food Poisoning, CDC Says

Little Progress Made In Fighting Food Poisoning, CDC Says

Newsy (Apr. 18, 2014) A new report shows rates of two foodborne infections increased in the U.S. in recent years, while salmonella actually dropped 9 percent. Video provided by Newsy
Powered by NewsLook.com
Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. Video provided by Newsy
Powered by NewsLook.com
Obama: 8 Million Healthcare Signups

Obama: 8 Million Healthcare Signups

AP (Apr. 17, 2014) President Barack Obama gave a briefing Thursday announcing 8 million people have signed up under the Affordable Care Act. He blasted continued Republican efforts to repeal the law. (April 17) Video provided by AP
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