Navigation Links
Rictor protein offers scientists a new molecular target for cancer therapies
Date:10/28/2010

BOSTON 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.


'/>"/>

Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
Source:Eurekalert

Related biology news :

1. Structural genomics accelerates protein structure determination
2. Too much SP2 protein turns stem cells into evil twin cancer cells
3. Elsevier introduces Protein Viewer, bringing science to life
4. LSUHSC study IDs proteins regulating water retention in salt-sensitive hypertension
5. Discovery of a mechanism that controls the expression of a protein involved in numerous cancers
6. Biodegradable foam plastic substitute made from milk protein and clay
7. Reaper protein strikes at mitochondria to kill cells
8. New clues to how cancer-related proteins plasmin, thrombin lose inhibition
9. UMMS researchers identify protein associated with sporadic ALS
10. Key difference in how TB bacteria degrade doomed proteins
11. Shifting forms: Penn study shows how variations of same protein affect immune response
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/26/2016)... LONDON , April 26, 2016 /PRNewswire/ ... Systems, a product subsidiary of Infosys (NYSE: ... partnership to integrate the Onegini mobile security platform ... http://photos.prnewswire.com/prnh/20151104/283829LOGO ) The integration ... security to access and transact across channels. Using ...
(Date:4/15/2016)... April 15, 2016  A new partnership announced ... accurate underwriting decisions in a fraction of the ... priced and high-value life insurance policies to consumers ... With Force Diagnostics, rapid testing (A1C, Cotinine ... readings (blood pressure, weight, pulse, BMI, and activity ...
(Date:4/13/2016)...  IMPOWER physicians supporting Medicaid patients in ... standard in telehealth thanks to a new partnership with ... IMPOWER patients can routinely track key health measurements, such ... and, when they opt in, share them with IMPOWER ... local retail location at no cost. By leveraging this ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... DIEGO , June 24, 2016 ... more sensitively detects cancers susceptible to PARP inhibitors ... circulating tumor cells (CTCs). The new test has ... HRD-targeted therapeutics in multiple cancer types. ... targeting DNA damage response pathways, including PARP, ATM, ...
(Date:6/23/2016)... ... June 23, 2016 , ... ... announce the launch of their brand, UP4™ Probiotics, into Target stores nationwide. The ... is proud to add Target to its list of well-respected retailers. This list ...
(Date:6/23/2016)... , June 23, 2016 Houston Methodist ... the Cy-Fair Sports Association to serve as their ... agreement, Houston Methodist Willowbrook will provide sponsorship support, ... connectivity with association coaches, volunteers, athletes and families. ... the Cy-Fair Sports Association and to bring Houston ...
(Date:6/23/2016)... FRANCISCO , June 23, 2016   EpiBiome ... has secured $1 million in debt financing from Silicon ... ramp up automation and to advance its drug development ... its new facility. "SVB has been an ... beyond the services a traditional bank would provide," said ...
Breaking Biology Technology: