Featured Research

from universities, journals, and other organizations

Restoring Function Of A Mutant Gene Without Altering DNA Might Be Possible

Date:
February 12, 2009
Source:
Fox Chase Cancer Center
Summary:
Researchers have demonstrated that it might be possible to treat genetic diseases, including some forms of cancer, by "rescuing" the misshapen, useless proteins produced by some mutant genes. The researchers demonstrate that manipulating the cellular amounts of a protein called Hsp70, they can give mutants another shot at refolding. The researchers believe it may be a means of hacking the natural biochemistry of cells to restore proteins otherwise lost to mutation.

Researchers detail how they were able to restore the function of a mutant human gene in a yeast model of disease by manipulating the available amounts of a so-called chaperone protein, named Hsp70, which helps amino acid chains fold into their proper protein form.
Credit: Image courtesy of Fox Chase Cancer Center

Researchers at Fox Chase Cancer Center have demonstrated that it might be possible to treat genetic diseases, including some forms of cancer, by "rescuing" the misshapen, useless proteins produced by some mutant genes.

Related Articles


In the current issue of the Journal of Biological Chemistry, available online now, researchers detail how they were able to restore the function of a mutant human gene in a yeast model of disease by manipulating the available amounts of a so-called chaperone protein, named Hsp70, which helps amino acid chains fold into their proper protein form.

"In some cases, despite a mutation, it is possible to coax a misfolded protein back into a functional conformation," says the paper's lead author Warren Kruger, Ph.D., senior faculty member at Fox Chase. "In essence, we're using Hsp70 to call a biochemical mulligan, a do-over."

"Hsp70 pulls a misfolded amino acid chain apart like a twisted rubber band and allows it to snap back into place, which we found can restore a significant percentage of proteins to working shape," Kruger says. "If this can be done in humans, it could represent a way of reducing the severity – or perhaps correcting – certain hereditary diseases, even some familial cancers."

Kruger and his colleagues are currently studying how to adapt these findings to human disease. While the study was done in a yeast model for human disease, humans possess at least nine members of the Hsp70 family of chaperones. Evidence suggests that it might be feasible to modify the chaperone environment in order to give Hsp70 better opportunities to rescue broken proteins. "The more chances we give Hsp70 proteins to try to 'fix' the output of mutant genes, the more chances are that they will succeed," Kruger says.

Very often, genetic mutations occur when errors in the DNA code substitute one amino acid for another. It is this sort of mutation that is at the center of a disease called cystathionine β-synthase (CBS) deficiency, an inherited metabolic disorder that the Kruger laboratory uses as a genetic model.

Through experiments performed by Laishram Singh, a post-doctoral fellow in the lab, Kruger learned that exposure to alcohol restored the function of a mutant human CBS protein expressed in genetically engineered yeast cells. This exposure activates heat shock proteins, like Hsp70, which help the cell respond to the shock, or damage, from stress. The sudden excess of Hsp70, in turn, had the side effect of rescuing mutated proteins in addition to those damaged by alcohol.

According to Kruger, Hsp70 works in equilibrium with another heat shock protein, Hsp26, as a sort of biochemical damage control system. While Hsp70 acts like a chaperone to restore the function of such proteins, Hsp26 targets the misfolded proteins to the proteosome, the "garbage disposal" of the cell. The two proteins, it seems, function in opposition, competing to clean up damaged proteins within cells.

The relationship between these two proteins may provide an opportunity for intervention, Kruger reasons. When Kruger and his colleagues removed the gene encoding Hsp26 from yeast, they saw a nine-fold increase in the amount of properly functioning human CBS protein. "If we can target Hsp26 and take it out of circulation, we might be able to give Hsp70 more room to operate," Kruger says.

Funding for this research comes from grants from the National Institutes of Health and the Commonwealth of Pennsylvania.


Story Source:

The above story is based on materials provided by Fox Chase Cancer Center. Note: Materials may be edited for content and length.


Cite This Page:

Fox Chase Cancer Center. "Restoring Function Of A Mutant Gene Without Altering DNA Might Be Possible." ScienceDaily. ScienceDaily, 12 February 2009. <www.sciencedaily.com/releases/2009/02/090211161946.htm>.
Fox Chase Cancer Center. (2009, February 12). Restoring Function Of A Mutant Gene Without Altering DNA Might Be Possible. ScienceDaily. Retrieved November 1, 2014 from www.sciencedaily.com/releases/2009/02/090211161946.htm
Fox Chase Cancer Center. "Restoring Function Of A Mutant Gene Without Altering DNA Might Be Possible." ScienceDaily. www.sciencedaily.com/releases/2009/02/090211161946.htm (accessed November 1, 2014).

Share This



More Plants & Animals News

Saturday, November 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Watch Baby Goose Survive A 400-Foot Cliff Dive

Watch Baby Goose Survive A 400-Foot Cliff Dive

Buzz60 (Oct. 31, 2014) For its nature series Life Story, the BBC profiled the barnacle goose, whose chicks must make a daredevil 400-foot cliff dive from their nests to find food. Jen Markham has the astonishing video. Video provided by Buzz60
Powered by NewsLook.com
World's Salamanders At Risk From Flesh-Eating Fungus

World's Salamanders At Risk From Flesh-Eating Fungus

Newsy (Oct. 31, 2014) The import of salamanders around the globe is thought to be contributing to the spread of a deadly fungus. Video provided by Newsy
Powered by NewsLook.com
Alcoholic Drinks In The E.U. Could Get Calorie Labels

Alcoholic Drinks In The E.U. Could Get Calorie Labels

Newsy (Oct. 31, 2014) A health group in the United Kingdom has called for mandatory calorie labels on alcoholic beverages in the European Union. Video provided by Newsy
Powered by NewsLook.com
Malaria Threat in Liberia as Fight Against Ebola Rages

Malaria Threat in Liberia as Fight Against Ebola Rages

AFP (Oct. 31, 2014) Focus on treating the Ebola epidemic in Liberia means that treatment for malaria, itself a killer, is hard to come by. MSF are now undertaking the mass distribution of antimalarials in Monrovia. Duration: 00:38 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


Plants & Animals

Earth & Climate

Fossils & Ruins

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