Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

‘Reaper’ protein strikes at mitochondria to kill cells

21.10.2010
Our cells live ever on the verge of suicide, requiring the close attention of a team of molecules to prevent the cells from pulling the trigger.

This self-destructive tendency can be a very good thing, as when dangerous precancerous cells are permitted to kill themselves, but it can also go horribly wrong, destroying brain cells that store memories, for instance.

Rockefeller University scientists are parsing this perilous arrangement in ever finer detail in hopes that understanding the basic mechanisms of programmed cell death, or apoptosis, will enable them eventually to manipulate the process to kill the cells we want to kill and protect the ones we don’t.

In experiments published last month in the Journal of Cell Biology, researchers led by postdoctoral associate Cristinel Sandu in Hermann Steller’s Strang Laboratory of Apoptosis and Cancer Biology drilled down on a protein aptly named Reaper, which was first described in a 1994 paper by Steller in Science. Under the right conditions,

Reaper interferes with molecules called inhibitor of apoptosis proteins (IAPs), which prevent the cell from irrevocably initiating its autodestruct sequence. By inhibiting these inhibitors, Reaper essentially takes the brakes off the process of apoptosis, pronouncing a cell’s death sentence. Other molecules called caspases then carry that sentence out.

“Like the grim reaper, Reaper is an announcer of death, but not the executioner,” says Steller, who is also a Howard Hughes Medical Institute investigator. “It’s like the key that starts the engine.”

Reaper and the other Drosophila IAP antagonists Hid and Grim are known to trigger apoptosis in flies, and related proteins serve a similar function in humans and other mammals. But exactly how and where Reaper initiates apoptosis has not been well understood. Sandu and colleagues bred genetically modified strains of flies that expressed variations on the Reaper protein specifically in flies’ eyes. This allowed them to assess the contribution of individual protein motifs to Reaper’s apoptosis inducing powers, and what they found was that a particular helical domain was crucial for the formation of Reaper complexes, and could be modified to be even more powerful than the regular protein. The more deadly Reaper variants were obvious by the damage caused to the flies’ eyes.

In a series of biochemical experiments, the researchers also found that Reaper must travel to the mitochondria, the cell’s energy factories, to effectively deliver its death sentence, and that to get there, it must hitch a ride on the Hid protein, with which it interacts. By tagging Hid and Reaper fluorescently, Sandu could visualize Hid and Reaper acting in a complex and gathering at the membrane of the mitochondria. When Reaper was engineered to go directly to the mitochondrial membrane, it resulted in a molecule that is far superior at triggering cell death than regular Reaper. Further experiments suggested that in a complex with Hid, Reaper is protected from degradation as the cells began to die.

“So now we have Hid and Reaper working very closely together,” Sandu says. “And the localization to the mitochondria is crucial to the initiation of apoptosis.” Drugs that mimic a small part of the function of Reaper are already in clinical trials. The discovery of a way to make Reaper a much better killer, namely by targeting it directly to the mitochondria, provides new avenues to explore for improving cancer therapies. “Adding this element that takes Reaper directly to the mitochondria is not something people would have thought of before this,” Steller says.

Brett Norman | EurekAlert!
Further information:
http://www.rockefeller.edu

More articles from Life Sciences:

nachricht Scientists discovered 20 new gnat species in Brazil
24.09.2018 | Estonian Research Council

nachricht Brought to light – chromobodies reveal changes in endogenous protein concentration in living cells
21.09.2018 | NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Scientists present new observations to understand the phase transition in quantum chromodynamics

The building blocks of matter in our universe were formed in the first 10 microseconds of its existence, according to the currently accepted scientific picture. After the Big Bang about 13.7 billion years ago, matter consisted mainly of quarks and gluons, two types of elementary particles whose interactions are governed by quantum chromodynamics (QCD), the theory of strong interaction. In the early universe, these particles moved (nearly) freely in a quark-gluon plasma.

This is a joint press release of University Muenster and Heidelberg as well as the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt.

Then, in a phase transition, they combined and formed hadrons, among them the building blocks of atomic nuclei, protons and neutrons. In the current issue of...

Im Focus: Patented nanostructure for solar cells: Rough optics, smooth surface

Thin-film solar cells made of crystalline silicon are inexpensive and achieve efficiencies of a good 14 percent. However, they could do even better if their shiny surfaces reflected less light. A team led by Prof. Christiane Becker from the Helmholtz-Zentrum Berlin (HZB) has now patented a sophisticated new solution to this problem.

"It is not enough simply to bring more light into the cell," says Christiane Becker. Such surface structures can even ultimately reduce the efficiency by...

Im Focus: New soft coral species discovered in Panama

A study in the journal Bulletin of Marine Science describes a new, blood-red species of octocoral found in Panama. The species in the genus Thesea was discovered in the threatened low-light reef environment on Hannibal Bank, 60 kilometers off mainland Pacific Panama, by researchers at the Smithsonian Tropical Research Institute in Panama (STRI) and the Centro de Investigación en Ciencias del Mar y Limnología (CIMAR) at the University of Costa Rica.

Scientists established the new species, Thesea dalioi, by comparing its physical traits, such as branch thickness and the bright red colony color, with the...

Im Focus: New devices based on rust could reduce excess heat in computers

Physicists explore long-distance information transmission in antiferromagnetic iron oxide

Scientists have succeeded in observing the first long-distance transfer of information in a magnetic group of materials known as antiferromagnets.

Im Focus: Finding Nemo's genes

An international team of researchers has mapped Nemo's genome

An international team of researchers has mapped Nemo's genome, providing the research community with an invaluable resource to decode the response of fish to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

"Boston calling": TU Berlin and the Weizenbaum Institute organize a conference in USA

21.09.2018 | Event News

One of the world’s most prominent strategic forums for global health held in Berlin in October 2018

03.09.2018 | Event News

4th Intelligent Materials - European Symposium on Intelligent Materials

27.08.2018 | Event News

 
Latest News

Matter falling into a black hole at 30 percent of the speed of light

24.09.2018 | Physics and Astronomy

NASA balloon mission captures electric blue clouds

24.09.2018 | Earth Sciences

New way to target advanced breast cancers

24.09.2018 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>