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

Join For Free

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 3,300+ scientific posters on ePosters
  • More than 4,800+ 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

Seeing RNA at the Nanoscale
MIT researchers have developed a new way to image proteins and RNA inside neurons of brain tissue.
Wednesday, July 06, 2016
Controlling RNA in Living Cells
Modular, programmable proteins can be used to track or manipulate gene expression.
Wednesday, April 27, 2016
Why Some Tumors Withstand Treatment
Mechanism uncovered that allows cancer cells to evade targeted therapies.
Thursday, March 17, 2016
Paving the Way for Metastasis
Cancer cells remodel their environment to make it easier to reach nearby blood vessels.
Tuesday, March 15, 2016
Synthetic Antibody Detects Proteins
Research could lead to nanosensors that recognize fibrinogen, insulin, or other biomarkers.
Friday, January 15, 2016
New Device Uses Carbon Nanotubes to Snag Molecules
Nanotube “forest” in a microfluidic channel may help detect rare proteins and viruses.
Tuesday, December 22, 2015
CRISPR-Cas9 Genome Editing Hurdle Overcome
Team re-engineers system to dramatically cut down on editing errors; improvements advance future human applications.
Thursday, December 03, 2015
A Natural Light Switch
MIT scientists identify and map the protein behind a light-sensing mechanism.
Tuesday, September 29, 2015
Biologists Find Unexpected Role for Amyloid-Forming Protein
Yeast protein could offer clues to how Alzheimer’s plaques form in the brain.
Monday, September 28, 2015
How Flu Viruses Gain The Ability To Spread
New study reveals the soft palate is a key site for evolution of airborne transmissibility.
Friday, September 25, 2015
Targeting DNA
Protein-based sensor could detect viral infection or kill cancer cells.
Tuesday, September 22, 2015
Targeting DNA
Protein-based sensor could detect viral infection or kill cancer cells.
Tuesday, September 22, 2015
Learning About Human Health Using Sewage
PhD student Mariana Matus studies human waste to understand individual and community health.
Thursday, September 17, 2015
Protein Found to Play a Key Role in Blocking Pathogen Survival
Calprotectin fends off microbial invaders by limiting access to iron, an important nutrient.
Wednesday, August 26, 2015
Real-Time Data for Cancer Therapy
Biochemical sensor implanted at initial biopsy could allow doctors to better monitor and adjust cancer treatments.
Thursday, August 06, 2015
Scientific News
Liquid Biopsies: Miracle Diagnostic or Next New Fad?
Thanks to the development of highly specific gene-amplification and sequencing technologies liquid biopsies access more biomarkers relevant to more cancers than ever before.
New Centre Offers Ultra-Speed Protein Analysis
UW-Madison researchers to establish development centre for next-gen protein measurement technologies.
Protein Nanocages Could Improve Drug Design and Delivery
HHMI scientists have designed and built 10 large protein icosahedra that are similar to viral capsids that carry viral DNA.
Virus Inspired Cell Cargo Ships
Virus-inspired container design may lead to cell cargo ships following construction of ten large, two-component, icosahedral protein complexes.
Protein Reinforces Growth of Damaged Muscles
Biologists have found a protein involved in stem cells that bolsters damaged muscle tissue growth - potential for muscle degeneration treatments.
Structure of Cold Virus Solved
Researchers have identified the structure of an elusive cold virus linked to child asthma and respiratory infections, providing the foundation for treating the virus.
New Protein Model Could Accelerate Drug Development
Stony Brook-led international research team creates ultra-fast approach to model protein interactions.
Researchers Can Control Genes Involved in Cancer
A new way to control the activity of a protein, that is often upregulated in cancer, has been discovered by Moffitt researchers through monoubiquitination mechanism.
Mitochondrial Role in Metastatic Cancer
Researchers have manipulated proteins, sourced from tumour cells, that are essential for maintaining tumour cells and in doing so, have significantly reduced the ability of cancer cells.
Liquid Biopsy Predicts Colon Cancer Recurrence
Scientists have used a genetic test that spots bits of cancer-related DNA circulating in the blood to accurately predict the likelihood of the disease’s return in some — but not all — of a small group of patients with early-stage colon cancer.
Scroll Up
Scroll Down
SELECTBIO

SELECTBIO Market Reports
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
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,800+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!