Researchers identify new, cancer-causing role for protein
August 27, 2009
Hui-Kuan Lin, Ph.D., is an assistant professor in M. D. Anderson's Department of Molecular and Cellular Oncology. Credit: M. D. Anderson
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.
Source: University of Texas M. D. Anderson Cancer Center (news : web)
-
A potential sugar fix for tumors
Apr 16, 2008 |
not rated yet |
0
-
An Achilles heel in cancer cells
Dec 08, 2008 |
not rated yet |
0
-
Cancer-related protein may play key role in Alzheimer's disease
Feb 28, 2008 |
not rated yet |
0
-
'Bridge' protein spurs deadliest stages of breast cancer
Feb 22, 2007 |
not rated yet |
0
-
M. D. Anderson team identifies new oncogene for brain cancer
Jul 02, 2007 |
not rated yet |
0
-
Engineers build first sub-10-nm carbon nanotube transistor
Feb 01, 2012 |
4.9 / 5 (33) |
30
-
Something old, something new: Evolution and the structural divergence of duplicate genes
Jan 31, 2012 |
4.6 / 5 (7) |
1
-
The hidden nanoworld of ice crystals: Revealing the dynamic behavior of quasi-liquid layers
Jan 30, 2012 |
5 / 5 (4) |
1
-
Stock market network reveals investor clustering
Jan 27, 2012 |
3.9 / 5 (23) |
8
-
Of microchemistry and molecules: Electronic microfluidic device synthesizes biocompatible probes
Jan 26, 2012 |
5 / 5 (2) |
0
-
Is Everyday Technology Killing Us?
Feb 08, 2012
-
Exercise and weight loss
Feb 08, 2012
-
Why do we have head aches? Our brains can't feel anything.
Feb 07, 2012
-
"The end of diseases" by David Agus, interview from Daily Show with Jon Stewart
Feb 04, 2012
-
Oncolytic adenovirus
Feb 04, 2012
-
Nutrition label stuffs and diets
Feb 02, 2012
- More from Physics Forums - Medical Sciences
More news stories
Starve a virus, feed a cure? Findings show how some cells protect themselves against HIV
A protein that protects some of our immune cells from the most common and virulent form of HIV works by starving the virus of the molecular building blocks that it needs to replicate, according to research published online ...
13 hours ago |
5 / 5 (3) |
0
|
Overeating may double risk of memory loss
New research suggests that consuming between 2,100 and 6,000 calories per day may double the risk of memory loss, or mild cognitive impairment (MCI), among people age 70 and older. The study was released today and will be ...
Medicine & Health / Neuroscience
10 hours ago |
5 / 5 (2) |
0
|
Declining health-care productivity in England: Who says so?
Reports that the National Health Service in England has been declining in productivity in the last decade appear to have been accepted as fact. However, a Viewpoint published Online First by The Lancet disputes this. The Vi ...
8 hours ago |
1 / 5 (1) |
1
Injured boomers beware: Know when to see doctor
(AP) -- It happened to nurse Jane Byron years after an in-line skating fall, business owner Haralee Weintraub while doing "men's" push-ups, and avid cyclist Gene Wilberg while lifting a heavy box.
15 hours ago |
5 / 5 (1) |
0
FDA-approved drug rapidly clears amyloid from the brain, reverses Alzheimer's symptoms in mice
Neuroscientists at Case Western Reserve University School of Medicine have made a dramatic breakthrough in their efforts to find a cure for Alzheimer's disease. The researchers' findings, published in the journal Science, show t ...
Medicine & Health / Neuroscience
Feb 09, 2012 |
4.9 / 5 (58) |
17
|
Scientists discover molecular secrets of 2,000-year-old Chinese herbal remedy
For roughly two thousand years, Chinese herbalists have treated Malaria using a root extract, commonly known as Chang Shan, from a type of hydrangea that grows in Tibet and Nepal. More recent studies suggest that halofuginone, ...
New method to examine batteries -- MRI from the inside
There is an ever-increasing need for advanced batteries for portable electronics, such as phones, cameras, and music players, but also to power electric vehicles and to facilitate the distribution and storage of energy derived ...
Google might launch Drive for cloud storage soon
(PhysOrg.com) -- Google's next big move, according to the Wall Street Journal, is a cloud storage service called Drive. Hardly first to the plate, Google is simply catching up to introducing its cloud reposi ...
A mitosis mystery solved: How chromosomes align perfectly in a dividing cell
Although the process of mitotic cell division has been studied intensely for more than 50 years, Whitehead Institute researchers have only now solved the mystery of how cells correctly align their chromosomes during symmetric ...
Lab study raises questions over nano-particle impact
Tests involving chickens have raised questions about the impact on health from engineered nano-particles, the ultra-fine grains commonly used in drugs and processed foods, scientists said on Sunday.
Researchers find extensive RNA editing in human transcriptome
In a new study published online in Nature Biotechnology, researchers from BGI, the world's largest genomics organization, reported the evidence of extensive RNA editing in a human cell line by analysis of RNA-seq data, demons ...