Navigation Links
Researchers identify new, cancer-causing role for protein
Date:8/27/2009

HOUSTON - The mainstay immune system protein TRAF6 plays an unexpected, key role activating a cell signaling molecule that in mutant form is associated with cancer growth, researchers at The University of Texas M. D. Anderson Cancer Center report in the Aug. 28 edition of Science.

"The mechanism that we discovered activates Akt and also contributes to hyperactivation of a mutant form of Akt found in breast, colon and other cancers," said senior author Hui-Kuan Lin, Ph.D., assistant professor in M. D. Anderson's Department of Molecular and Cellular Oncology.

Akt is a signaling protein that plays a central role in numerous biological functions, including cell growth and programmed cell death, or apoptosis, Lin said. Deregulated Akt expression has been found to contribute to cancer development.

"Our novel findings are that Akt undergoes ubiquitination to be activated, and that TRAF6 regulates that process. We've found that TRAF6 is not just involved in the innate immune response, but plays a role in cell growth and carcinogenesis," Lin said.

Ubiquitins are regulatory proteins that work by binding to other proteins. While ubiquitins are best known for marking a defective protein for death by the cell's proteasome complex, Lin said, ubiquitination of Akt is not tied to the proteasome. Ubiquitins are transferred to target proteins by another set of proteins called ligases.

Akt resides in the cell's cytoplasm and must be recruited to the cell membrane in order to be activated by attachment of phosphate groups to specific locations on the protein, Lin explained. The mechanism that gets Akt to the membrane had not been understood.

Because one type of ubiquitination involves protein movement, Lin's team launched a series of cell line experiments that showed Akt is ubiquitinated, and in a way not involving the proteasome.

Screening a different class of ubiquitin ligases showed that overexpression of TRAF6 E3 ligase promotes Akt ubiquitination. Subsequent experiments showed that Akt ubiquitination is required to move Akt to the cell membrane, and leads to Akt's phosphorylation and activation.

Next, the researchers analyzed a mutant form of Akt implicated in human breast cancer, finding that increased Akt ubiquitination contributes to the hyperactivation of Akt in the mutant cells. "We discovered this oncogenic Akt mutant is hyperubiquitinated," Lin said. "If you disrupt its ubiquitination, you deactivate the mutant."

The team found depleting TRAF6 in prostate cancer cells reduced Akt activation. And mice with TRAF6 knocked down developed smaller prostate cancer tumors than those with active TRAF6. "We believe that TRAF6 is a previously unrecognized oncogene and is a new potential target for treating human cancers," Lin said.

Having discovered this Akt activation pathway, Lin and colleagues are now trying to identify the enzyme that normally turns it off.


'/>"/>

Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

Related medicine news :

1. Carnegie Mellon Researchers Develop Novel Tool to Rank Death Rates
2. Researchers evaluate resistance training for diabetes prevention
3. Researchers find that employees who are engaged in their work have happier home life
4. U-M researchers discover therapeutic target that could help patients with pulmonary fibrosis
5. UCSF Researchers Identify Two Key Pathways in Adaptive Response
6. Alcohol advertising reaching too many teens on cable TV, researchers say
7. NIH researchers identify key factor that stimulates brain cancer cells to spread
8. Pitt researchers harness carbon nanomaterials for drug delivery systems, oxygen sensors
9. Microsoft Rogue Internet Pharmacy Problem Fixed? Not So Fast, Say Researchers
10. Researchers identify potential new avenue to attack cancer
11. Researchers find alcoholics display abnormal brain activity when processing facial expressions
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Researchers identify new, cancer-causing role for protein
(Date:5/31/2016)... ... May 31, 2016 , ... Twenty years ago it was revolutionary: ... trying to silence the voices they hear. But this approach has proven transformative, both ... method has steadily gained credibility and now is used around the world, but it ...
(Date:5/31/2016)... Eden Prairie, MN (PRWEB) , ... May 31, 2016 , ... ... accreditation from the American Association for Laboratory Accreditation (A2LA) to include ISO 594-1 and ... the most common means of achieving a leak-free connection between two medical devices (e.g. ...
(Date:5/31/2016)... ... May 31, 2016 , ... Effective leaders not only drive service ... as a whole. On June 2, Northbound CEO Mike Neatherton and COO Paul Alexander ... presenting the opening plenary on “Leadership: The Journey to Authenticity” with Onsite Workshops CEO ...
(Date:5/31/2016)... ... ... The Global Wellness Summit (GWS), an annual conference for international leaders ... spa and beauty in Europe. The organization asked its partner experts in Europe - ... - to forecast where wellness is headed in Europe. Predictions range from European nations ...
(Date:5/31/2016)... Montana (PRWEB) , ... May 31, 2016 , ... Spectrum ... Lift. This new lift has been designed and built with the user in mind. ... of aquatic consultants have informed us that an ADA 400 lbs lift is a ...
Breaking Medicine News(10 mins):
(Date:5/31/2016)... , May 31, 2016 The ... is progressing at a CAGR of 10.6% within a ... valued at US$0.46 bn in 2013. Owing to favorable ... to reach US$0.88 bn by the end of this ... from the market,s holistic representation in a research report ...
(Date:5/31/2016)... ZIONA, Israel , May 31, ... medicine company utilizing its proprietary plant-based rhCollagen technology for ... authorization from the Chief Scientist of Israel,s ... of its NIS 12 million development project for 2016. The ... higher than last year,s authorized grant, which totaled NIS ...
(Date:5/30/2016)... India , May 30, 2016 /PRNewswire/ ... market research report "Healthcare Biometrics Market by ... (Signature, Voice)), Multifactor, Multimodal), Application (Workforce Management), ... Forecast to 2021", published by MarketsandMarkets, the ... Million by 2021 from USD 1,182.6 Million ...
Breaking Medicine Technology: