Navigation Links
Researchers identify new, cancer-causing role for protein

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
University of Texas M. D. Anderson Cancer Center

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:
Related Image:
Researchers identify new, cancer-causing role for protein
(Date:11/24/2015)... VA (PRWEB) , ... November 24, 2015 , ... Preparing ... 1:30 p.m. – 3:00 p.m. EST, , FDA has long asserted ... CLIA regulations apply to performing the tests and do not meet the device regulations. ...
(Date:11/24/2015)... (PRWEB) , ... November 24, 2015 , ... ... advisory organization, is pleased to welcome Winter-Dent & Company as its newest Partner ... day one to become a client's most trusted advisor regardless of whether that ...
(Date:11/24/2015)... ... November 24, 2015 , ... With Thanksgiving right around the ... safety tips to help protect your family and vehicle. , According to the National ... Thanksgiving holiday weekend. Amica is sharing the following safety tips from the NHTSA: ...
(Date:11/24/2015)... ... November 24, 2015 , ... Dr. Rodney E. Willey , has answered a new ... Center for Sleep Disorders, provides treatment for snoring and sleep apnea through oral ... Koala Center for Sleep Disorders in the US, one of four in the Illinois area. ...
(Date:11/24/2015)... ... 24, 2015 , ... Dr. Kevin Day, local family chiropractor in Warsaw ... this holiday season. During the Indiana winter months, Vitamin D deficiency can lead ... at AlignLife want to help provide the tools needed to combat it this year! ...
Breaking Medicine News(10 mins):
(Date:11/24/2015)... , Nov. 24, 2015  BioPlast Manufacturing, ... the medical research, clinical diagnostic and biotech environments, ... leading manufacturer of quality petri dishes. This acquisition ... clients a platform of products that are designed ... with the highest quality.  ...
(Date:11/24/2015)... brand Revo has debuted a new capsule collection ... Bono as part of the " Buy Vision, Give Sight ... than 5 million people by 2020.  --> ... sale of every pair of Revo sunglasses, including Bono,s "Vision ... to the "Buy Vision, Give Sight" initiative. These funds will ...
(Date:11/24/2015)... USA , Inc. (OTCQB: WCUI), today provided an update ... to targeted dermatology markets in Boston , ... North Carolina . This follows earlier shipments to the ... , and New York dermatology markets. ... reported on October 1, 2015 will be realized in the pending quarter, ...
Breaking Medicine Technology: