Navigation Links
New mechanism for cancer progression discovered by UNC and Harvard researchers
Date:11/27/2012

The protein Ras plays an important role in cellular growth control. Researchers have focused on the protein because mutations in its gene are found in more than 30 percent of all cancers, making it the most prevalent human oncogene.

University of North Carolina Lineberger Comprehensive Cancer Center and Harvard researchers have discovered an alternative mechanism for activating Ras that does not require mutation or hormonal stimulus. In healthy cells, Ras transmits hormone signals into the cell that prompt responses such as cell growth and the development of organs and tissues. A mutation on the RAS gene can chronically activate those signals, leading to tumor initiation and progression.

In an article published on-line in a November issue of Nature Structural and Molecular Biology, the UNC and Harvard teams discovered that modification of Ras at a specific site with a small protein known as ubiquitin can also lock Ras into an active signaling state. Thus, modification of Ras with a single ubiquitin a process known as monoubiquitination - switches Ras to an active signaling state by disrupting the action of another protein known as the GTPase activating protein, or GAP. Work by two of the papers co-authors, Atsuo Sasaki and Lewis Cantley of Harvard, had previously found evidence for Ras's potential to become activated and promote Ras-mediated tumorigenesis by monoubiquitination.

Because of the strong link between Ras and cancer, Ras should be an attractive target for drug discovery efforts. Despite considerable efforts at developing treatments targeting the protein, Ras itself is now considered to be 'undruggable', leading researchers to try new approaches to developing drugs that target activated Ras. This could lead to benefits beyond cancer therapies, as the RAS gene has also been linked to developmental disorders such as Noonan syndrome, Costello syndrome and autoimmune lymphoproliferative syndrome.

Lead researcher Rachael Baker, a PhD candidate doing joint work in the labs of Henrik Dohlman, PhD, professor of pharmacology and vice chair of biochemistry and biophysics and Sharon Campbell, PhD, professor of biochemistry and biophysics at UNC, developed a novel method to modify Ras with ubiquitin and then subsequently characterized how ubiquitin modification can lead to Ras activation.

The attachment of ubiquitin to Ras at a specific site leads to Ras activation, much like with an oncogenic mutation, leading to an increased potential for cancer formation. Baker notes that the reaction can be reversed by enzymes in the cell that remove ubiquitin, making these enzymes possible targets for future pharmaceutical research.

"Establishing how Ras is activated by ubiquitin is just the first step in understanding this novel mechanism of cellular regulation." said Campbell.

The researchers next step will be to obtain a more detailed understanding of its role in cancer progression, first in cells and in animals and eventually in cancer patients.


'/>"/>

Contact: William Davis
william_davis@med.unc.edu
919-962-3405
University of North Carolina Health Care
Source:Eurekalert

Related medicine news :

1. Joslin scientists identify important mechanism that affects the aging process
2. Researchers gain better understanding of mechanism behind tau spreading in the brain
3. Aggregating instead of stabilizing: New insights into the mechanisms of heart disease
4. Study supports urate protection against Parkinsons disease, hints at novel mechanism
5. Probing the mechanism of ADAM28-mediated cancer metastasis
6. Fruit flies reveal mechanism behind ALS-like disease
7. Scientists discover mechanism that promotes lung cancer growth and survival
8. Abnormal gene product associated with prostate cancer generated by unusual mechanism
9. New mechanism of bacterial pathogenesis discovered
10. Scientists identify new cancer stem cell mechanism
11. Zebrafish reveal promising mechanism for healing spinal cord injury
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... ... June 27, 2016 , ... A ... revolutionize the emergency ambulance transport experience for the millions of people who require ... has disrupted the taxi industry through the use of technology. Now, SmartEMS has ...
(Date:6/26/2016)... ... 2016 , ... On June 10-11, 2016, A Forever Recovery, a holistic treatment ... Longest Breakfast Table in Battle Creek, MI, where the rehabilitation facility is located. This ... of the world’s leading providers of cereal and other breakfast foods. Its residents often ...
(Date:6/26/2016)... ... 26, 2016 , ... Brent Kasmer, a legally blind and certified personal trainer is helping to ... app. The fitness app plans to fix the two major problems leading the fitness industry ... fits all type program , They don’t eliminate all the reasons people quit ...
(Date:6/25/2016)... ... June 25, 2016 , ... Austin residents seeking Mohs ... College of Mohs Surgery and to Dr. Russell Peckham for medical and surgical dermatology. ... treatment for skin cancer. The selective fellowship in Mohs Micrographic Surgery completed by Dr. ...
(Date:6/25/2016)... ... ... First Choice Emergency Room , the largest network of independent freestanding ... of its new Mesquite-Samuell Farm facility. , “We are pleased to announce Dr. ... James M. Muzzarelli, Executive Medical Director of First Choice Emergency Room. , Dr. ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... INDIANAPOLIS , June 23, 2016 ... Tomorrow,s Leaders Scholarship is any indication, the future is ... online at www.diabetesscholars.org by the Diabetes Scholars ... in the way of academic and community service excellence. ... program since 2012, and continues to advocate for people ...
(Date:6/23/2016)... -- Guerbet announced today that it has been named a ... One of 12 suppliers to receive the ... of Premier members through exceptional local customer service and ... lower costs. "We ... customer service from Premier," says Massimo Carrara , ...
(Date:6/23/2016)... Tenn. , June 23, 2016 /PRNewswire/ ... automating, integrating and transforming the patient payment ... of several innovative new products and services ... of its revenue cycle offerings. These award-winning ... more efficient workflows, remain compliant in an ...
Breaking Medicine Technology: