Featured Research

from universities, journals, and other organizations

Rictor protein offers scientists a new molecular target for cancer therapies

Date:
October 28, 2010
Source:
Beth Israel Deaconess Medical Center
Summary:
The discovery that a protein called Rictor plays a key role in destroying a close cousin of the AKT oncogene could provide scientists with a new molecular target for treating certain cancers, including breast cancer.

The discovery that a protein called Rictor plays a key role in destroying a close cousin of the AKT oncogene could provide scientists with a new molecular target for treating certain cancers, including breast cancer.

Described in the September 2010 issue of the journal Molecular Cell, the study was led by scientists at Beth Israel Deaconess Medical Center (BIDMC).

The oncogenic cousin, known as SGK1, resembles the widely known AKT oncogene in structure, according to the study's senior author Wenyi Wei, PhD, of the Department of Pathology at BIDMC and Assistant Professor of Pathology at Harvard Medical School (HMS).

"If we put the two proteins together, they are very similar," explains Wei. "But in one important way they are very different. AKT is stable, it lives for a long time. But SGK1 has a very short lifespan, and proteins with short lifespans tend to be powerful. Everybody's eye [has been] on AKT, but you have to wonder if this little cousin of AKT can do all the things AKT does." Wei and his team, therefore, set out to better understand how cells control SGK1.

Previous research showed that the protein Rictor forms a multi-protein complex called mTORC2 that activates both AKT and SGK1. Wei's team cultured cells lacking Rictor to observe the effect on SGK1. Surprisingly, they found that SGK1 levels increased.

"We said, that cannot be," notes Wei. "How could we get rid of the protein kinase that activates SGK1 and still have the SGK1 levels be heightened?"

They found their answer when they observed that the cells weren't producing more SGK1; rather, SGK1 was living longer. This suggested to the scientists that Rictor might be playing a role in the destruction of SGK1. And, in subsequent experiments, Wei found that SGK1 is indeed held in check by a protein complex made up of Rictor, Cullin-1, Rbx1, and possibly other components. The protein complex forms a cellular garbage collector called an E3 ligase that degrades SGK1 so it cannot build up.

"The protein Rictor is modular and multifunctional," said Wei. "Its function depends on its partners." This observation suggests that some proteins may act like a central machine that can work with a variety of attachments, the same way a construction vehicle can change its function depending on whether it's wielding a bulldozer or a crane. "With further study," he adds, "we may find more proteins [like Rictor] that have multiple functions. When a cell makes a protein this big, isn't it a waste of energy to have only one function?"

Wei's team further observed that once SGK1 begins to accumulate, it turns right around and interrupts the Rictor-Cullin1 complex, stifling it's garbage collection activities. "It looks like a positive feedback loop that serves to increase SGK1," says Wei.

"The novelty and significance of this work lies in the discovery of a role for Rictor in destroying SGK1, a key regulator of cell growth and cell death that is frequently associated with human cancers," said Marion Zatz, PhD, who manages cell cycle grants at the National Institutes of Health (NIH). "The finding suggests that faulty regulation of Rictor may play a part in some forms of cancer, and could offer us a new target for treating the disease."

While the exact role of SGK1 in tumor growth isn't yet clear, Wei speculates that SGK1 may play a role in cancer by hijacking a cell's metabolism, just as its close cousin AKT does. "This mechanism we discovered may be part of what drives overexpression of SGK1," he adds.

This study was supported, in part, by grants from the National Institutes of Health and by a DOD Prostate New Investigator Award to Wenyi Wei. Wei is a Kimmel Scholar, V Scholar and Karin Grunebaum Cancer Research Foundation Fellow.

Study coauthors include BIDMC investigators Daming Gao (first author), Lixin Wan, Hiroyuki Inuzuka, Anders Berg, Alan Tseng, Shavali Shaik, Jessica Gasser and Alex Toker; Bo Zhai, Steven Gygi, Eric Bennett, and J. Wade Harper of Harvard Medical School; and Adriana Tron and James DeCaprio of the Dana-Farber Cancer Institute.


Story Source:

The above story is based on materials provided by Beth Israel Deaconess Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Daming Gao, Lixin Wan, Hiroyuki Inuzuka, Anders H. Berg, Alan Tseng, Bo Zhai, Shavali Shaik, Eric Bennett, Adriana E. Tron, Jessica A. Gasser. Rictor Forms a Complex with Cullin-1 to Promote SGK1 Ubiquitination and Destruction. Molecular Cell, 2010; 39 (5): 797 DOI: 10.1016/j.molcel.2010.08.016

Cite This Page:

Beth Israel Deaconess Medical Center. "Rictor protein offers scientists a new molecular target for cancer therapies." ScienceDaily. ScienceDaily, 28 October 2010. <www.sciencedaily.com/releases/2010/10/101028141803.htm>.
Beth Israel Deaconess Medical Center. (2010, October 28). Rictor protein offers scientists a new molecular target for cancer therapies. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2010/10/101028141803.htm
Beth Israel Deaconess Medical Center. "Rictor protein offers scientists a new molecular target for cancer therapies." ScienceDaily. www.sciencedaily.com/releases/2010/10/101028141803.htm (accessed July 25, 2014).

Share This




More Health & Medicine News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com
Condemned Man's US Execution Takes Nearly Two Hours

Condemned Man's US Execution Takes Nearly Two Hours

AFP (July 24, 2014) America's death penalty debate raged Thursday after it took nearly two hours for Arizona to execute a prisoner who lost a Supreme Court battle challenging the experimental lethal drug cocktail. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
Can Watching TV Make You Feel Like A Failure?

Can Watching TV Make You Feel Like A Failure?

Newsy (July 24, 2014) A study by German researchers claims watching TV while you're stressed out can make you feel guilty and like a failure. 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:
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