Featured Research

from universities, journals, and other organizations

New metabolic pathway involved in cell growth and implicated in cancer as well as metabolic disorders identified

Date:
August 1, 2013
Source:
Sanford-Burnham Medical Research Institute
Summary:
Researchers now have a more complete picture of one particular pathway that can lead to cancer and diabetes. Scientists uncovered how a protein called p62 has a cascade affect in regulating cell growth in response to the presence of nutrients such as amino acids and glucose.

Deciphering the body's complex molecular pathways that lead to disease when they malfunction is highly challenging. Researchers at Sanford-Burnham Medical Research Institute now have a more complete picture of one particular pathway that can lead to cancer and diabetes. In the study published by Molecular Cell, the scientists uncovered how a protein called p62 has a cascade affect in regulating cell growth in response to the presence of nutrients such as amino acids and glucose. Disrupting this chain may offer a new approach to treating disease.

Related Articles


The protein p62 interacts with another protein called TRAF6 to activate a protein complex called mTORC1. In fact, researchers have found that mTORC1, also known as mammalian target of rapamycin complex 1, is highly activated in cancer cells. The pathway that controls mTORC1 activation is also important for metabolic homeostasis (i.e., stability). When the pathway malfunctions, metabolic disorders such as diabetes can result and tumors can progress.

About a year ago, Maria Diaz-Meco, Ph.D., Jorge Moscat, Ph.D., and their colleagues had identified that p62 is an important player in this complex pathway. But they didn't know how. Their new study shows that p62 activates mTORC1 through TRAF6.

"The mTORC1 pathway is a major complex important not only for cancer but also for metabolic homeostasis," said Diaz-Meco. "For that reason, it's very important to unravel the mechanism that controls how mTORC1 responds to the different signals."

"mTORC1 responds to many growth signals," she added, "but the specific mechanisms that channel the activation of mTORC1 by nutrients such as amino acids and glucose are still not completely understood. Our goal was to discern the specific mechanisms that regulate this important pathway."

The researchers found that TRAF6 plays a role in activating mTORC1 by molecularly modifying it in a process called ubiquitination. TRAF6, meanwhile, itself becomes activated in the presence of amino acids. "When you have a diet high in meat, the concentration of amino acids in your blood increases, and that's a way to activate this pathway," Moscat said. This can have tremendous implications not only for diabetes, but also for cancer-cell proliferation, which needs a constant supply of nutrients to grow.

More work is needed to fully understand the pathway, but the researchers next plan is to find ways to disrupt the interaction between p62 and TRAF6, with the ultimate goal of inactivating mTORC1 and therefore controlling cancer progression. "Because mTORC1 is a highly important protein that regulates growth, therapies aimed at blocking mTORC1 activation may offer a new approach to treating disease," Diaz-Meco said.

This work was supported by grants from the U.S. National Institutes of Health (grants R01CA132847, R01AI072581, R01DK088107, R01CA134530M).

Juan F. Linares, Sanford-Burnham; Angeles Duran, Sanford-Burnham; Tomoko Yajima, Sanford-Burnham; Manolis Pasparakis, Institute for Genetics, University of Cologne (Germany); Jorge Moscat, Sanford-Burnham; and Maria T. Diaz-Meco, Sanford-Burnham.


Story Source:

The above story is based on materials provided by Sanford-Burnham Medical Research Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. JuanF. Linares, Angeles Duran, Tomoko Yajima, Manolis Pasparakis, Jorge Moscat, MariaT. Diaz-Meco. K63 Polyubiquitination and Activation of mTOR by the p62-TRAF6 Complex in Nutrient-Activated Cells. Molecular Cell, 2013; DOI: 10.1016/j.molcel.2013.06.020

Cite This Page:

Sanford-Burnham Medical Research Institute. "New metabolic pathway involved in cell growth and implicated in cancer as well as metabolic disorders identified." ScienceDaily. ScienceDaily, 1 August 2013. <www.sciencedaily.com/releases/2013/08/130801125030.htm>.
Sanford-Burnham Medical Research Institute. (2013, August 1). New metabolic pathway involved in cell growth and implicated in cancer as well as metabolic disorders identified. ScienceDaily. Retrieved November 24, 2014 from www.sciencedaily.com/releases/2013/08/130801125030.htm
Sanford-Burnham Medical Research Institute. "New metabolic pathway involved in cell growth and implicated in cancer as well as metabolic disorders identified." ScienceDaily. www.sciencedaily.com/releases/2013/08/130801125030.htm (accessed November 24, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, November 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

AFP (Nov. 23, 2014) The arable district of Kenema in Sierra Leone -- at the centre of the Ebola outbreak in May -- has been under quarantine for three months as the cocoa harvest comes in. Duration: 01:32 Video provided by AFP
Powered by NewsLook.com
Don't Fall For Flu Shot Myths

Don't Fall For Flu Shot Myths

Newsy (Nov. 23, 2014) Misconceptions abound when it comes to your annual flu shot. Medical experts say most people older than 6 months should get the shot. Video provided by Newsy
Powered by NewsLook.com
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

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