Corporate Banner
Satellite Banner
Proteomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Study IDs Key Protein for Cell Death

Published: Tuesday, May 14, 2013
Last Updated: Tuesday, May 14, 2013
Bookmark and Share
Findings may offer a new way to kill cancer cells by forcing them into an alternative programmed-death pathway.

When cells suffer too much DNA damage, they are usually forced to undergo programmed cell death, or apoptosis. However, cancer cells often ignore these signals, flourishing even after chemotherapy drugs have ravaged their DNA.

A new finding from MIT researchers may offer a way to overcome that resistance: The team has identified a key protein involved in an alternative death pathway known as programmed necrosis. Drugs that mimic the effects of this protein could push cancer cells that are resistant to apoptosis into necrosis instead.

While apoptosis is a tightly controlled procedure that breaks down and disposes of the dying cell in a very orderly way, necrosis is a messier process in which the cell’s membrane ruptures and its contents spill out.

“People really used to think of necrosis as cells just falling apart, that it wasn’t programmed and didn’t require gene products to make it happen,” says Leona Samson, a member of MIT’s Center for Environmental Health Sciences and Koch Institute for Integrative Cancer Research. “In the last few years it has become more clear that this is an active process that requires proteins to take place.”

In the May 10 online edition of the journal Genes and Development, Samson and colleagues report that a protein known as ALKBH7 plays a key role in controlling the programmed necrosis pathway. Dragony Fu, a former postdoc in Samson’s lab, is the paper’s lead author, and postdoc Jennifer Jordan is also an author.

Unexpected findings

ALKBH7 belongs to a family of proteins first discovered in E. coli about a dozen years ago as part of a DNA-repair mechanism. In humans, there are nine different ALKBH proteins, which Samson’s lab has been studying for several years.

Most of the mammalian ALKBH proteins appear to be involved in DNA repair, similar to the original E. coli version. In particular, they respond to DNA damage caused by alkylating agents. These agents can be found in pollutants such as fuel exhaust and tobacco smoke, and are also used to treat cancer.

In the new paper, Samson, a professor of biology and biological engineering, and her colleagues found that ALKBH7 has an unexpected effect. When the researchers lowered ALKBH7 levels in human cells grown in the lab, those cells were much more likely to survive DNA damage than cells with normal ALKBH7 levels. This suggests that ALKBH7 actually promotes cell death.

“That was a surprising finding, because previously all of these ALKBH proteins were shown to be helping the cell survive when exposed to damage,” says Fu, who is now a visiting research fellow at the University of Zurich.

Upon further investigation, the researchers found that when healthy cells suffer massive DNA damage from alkylating agents, they enter the programmed necrosis pathway. Necrosis, which can also be initiated by bacterial or viral infection, is believed to help the body’s immune system detect threats.

“When dying cells release their contents during necrosis, it serves as a warning signal for your body that there is a virus there and recruits macrophages and other immune cells to the area,” Fu says.

Potential drug targets

The findings suggest that when DNA is so badly harmed that cells can’t repair it, the programmed necrosis pathway kicks in to prevent cells with major genetic damage from potentially become cancerous.

Other researchers have shown that some types of cancer cells have much lower ALKBH7 levels than normal cells. This suggests that the cancer cells have gained the ability to evade programmed necrosis, helping them to survive, Fu says.

The necrosis pathway appears to be initiated by an enzyme called PARP, which becomes hyperactive following DNA damage and shuts down the cell’s production of two molecules that carry energy, ATP and NAD. The MIT team found that ALKBH7 prevents ATP and NAD levels from returning to normal by disrupting the function of mitochondria — the cell structures that generate energy for a cell.

Without an adequate supply of those critical energy-carrying molecules, the cell cannot survive and undergoes necrosis. In cells that lack ALKBH7, ATP and NAD levels rebound, and the cells survive, carrying a heavy burden of DNA damage.

The researchers are now investigating the molecular details of the programmed necrosis pathway in hopes of identifying ways to activate it in cancer cells.

“The observations reported in this paper open up the possibility that novel treatments could be developed to treat tumors that are relatively resistant to killing via the apoptotic pathway,” says Ashok Bhagwat, a professor of chemistry at Wayne State University who was not part of the research team.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Bacterial Computing
The “friendly” bacteria inside our digestive systems are being given an upgrade, which may one day allow them to be programmed to detect and ultimately treat diseases such as colon cancer and immune disorders.
Monday, July 13, 2015
New Approach to Global Health Challenges
MIT’s Institute for Medical Engineering and Science brings many tools to the quest for new disease treatments and diagnostic devices.
Friday, September 27, 2013
Why Tumors Become Drug-Resistant
New findings could lead to drugs that fight back when tumors don’t respond to treatment.
Monday, August 12, 2013
Reducing Caloric Intake Delays Nerve Cell Loss
Study points to role of protein in anti-aging benefits of calorie restriction.
Thursday, May 23, 2013
Device Finds Stray Cancer Cells in Patients’ Blood
A microfluidic device that captures circulating tumor cells could give doctors a noninvasive way to diagnose and track cancers.
Wednesday, April 10, 2013
Sorting out the Structure of a Parkinson’s Protein
Computer modeling may resolve conflicting results and offer hints for new drug-design strategies.
Tuesday, April 02, 2013
New Technology May Enable Earlier Cancer Diagnosis
Nanoparticles amplify tumor signals, making them much easier to detect in the urine.
Friday, December 21, 2012
Evolution: It’s All in How You Splice It
MIT biologists find that alternative splicing of RNA rewires signaling in different tissues and may often contribute to species differences.
Friday, December 21, 2012
Researchers Synthesize a New Kind of Silk Fiber
Scientists find that music can help fine-tune the material’s properties.
Thursday, November 29, 2012
New Injectable Gels Toughen up after Entering the Body
These more durable gels could find applications in drug delivery and tissue engineering.
Friday, November 16, 2012
A Step Toward Stronger Polymers
Counting loops that weaken materials could help researchers eliminate structural flaws.
Tuesday, November 06, 2012
A New Glow for Electron Microscopy
Protein-labeling technique allows high-resolution visualization of molecules inside cells.
Monday, October 22, 2012
Oscillating Microscopic Beads Could be Key to Biolab on a Chip
MIT team finds way to manipulate and measure magnetic particles without contact, potentially enabling multiple medical tests on a tiny device.
Tuesday, September 25, 2012
Strategies Converge on Target in Rare Leukemia
In order to treat AMKL in patients who do not respond to current therapies, researchers need a protein target at which to take aim.
Wednesday, August 08, 2012
Researchers Build a Toolbox for Synthetic Biology
Engineers design new proteins that can help control novel genetic circuits in cells.
Friday, August 03, 2012
Scientific News
TOPLESS Plants Provide Clues to Human Molecular Interactions
Scientists at Van Andel Research Institute have revealed an important molecular mechanism in plants that has significant similarities to certain signaling mechanisms in humans, which are closely linked to early embryonic development and to diseases such as cancer.
Toxin from Salmonid Fish has Potential to Treat Cancer
Researchers from the University of Freiburg decode molecular mechanism of fish pathogen.
Long-sought Discovery Fills in Missing Details of Cell 'Switchboard'
A biomedical breakthrough reveals never-before-seen details of the human body’s cellular switchboard that regulates sensory and hormonal responses.
Rice Disease-Resistance Discovery Closes the Loop for Scientific Integrity
Researchers reveal how disease resistant rice detects and responds to bacterial infections.
The Mystery of the Instant Noodle Chromosomes
Researchers from the Lomonosov Moscow State University evaluated the benefits of placing the DNA on the principle of spaghetti.
New Mussel-Inspired Surgical Protein Glue
Korean scientists have developed a light-activated, mussel protein-based bioadhesive that works on the same principles as mussels attaching to underwater surfaces and insects maintaining structural balance and flexibility.
Vital Protein in Healthy Fertilization Process Identified
Researchers at the National Institutes of Health have discovered a protein that plays a vital role in healthy egg-sperm union in mice.
Teeth Reveal Lifetime Exposures to Metals, Toxins
Researchers have identified dental biomarkers to reveal links between early iron exposure and late life brain diseases.
View of Bacterial Pump at the Atomic Level
Researchers have determined the structure of a simple but previously unexamined pump that controls the passage of proteins through a bacterial cell membrane, an achievement that offers new insight into the mechanics that allow bacteria to manipulate their environments.
An Innovative Algorithm to Decipher How Drugs Work Inside the Body
Researchers at Columbia University Medical Center (CUMC) have developed a computer algorithm that is helping scientists see how drugs produce pharmacological effects inside the body.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!