Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Enzyme That Mutates Antibodies Also Targets Cancer-Causing Gene

15.12.2008
Rockefeller University scientists have found that the same enzyme that enables an effective immune response is also responsible for the DNA breaks that cause lymphomas.

The human immune system is in a perpetual state of self-experimentation. It expertly mutates and shuffles the DNA of its own cells to evolve new defenses against the vast array of microbes that try to invade our bodies. But when the genetic experiment goes awry, the result can be a deadly cancer.

Now, Rockefeller University scientists have discovered that the same enzyme that enables the immune system’s defensive creativity is also responsible for a particular genetic malfunction -- a translocation of one piece of DNA to the wrong chromosome -- that causes Burkitt’s lymphoma. The findings, to be published in the December 12 edition of Cell, suggest the enzyme, called activation-induced deaminase (AID), is probably involved in a broader range of cancers as well.

“We strongly suspect that many or all of the translocations of human lymphomas in mature B cells are the product of this enzyme,” says Michel C. Nussenzweig, Sherman Fairchild Professor and head of the Laboratory of Molecular Immunology. “And there’s more and more data to show that it may be involved in other cancers as well. It’s been identified in stomach cancers, for instance.”

A very specific translocation causes Burkitt’s lymphoma, a cancer that plagues children in equatorial Africa. It involves a DNA break in an immune system antibody gene and the much more rare break in a cancer-promoting gene called c-myc. Previous work had shown that AID was responsible for breaking antibody genes but not c-myc. In fact, scientists thought a host of other factors might be involved in the c-myc break, but AID had been all but ruled out.

Despite the prior studies, Davide Robbiani, a research associate in Nussenzweig’s lab and a Leukemia and Lymphoma Society Fellow, believed AID was the culprit. To prove it, he and his colleagues started by deleting the promoter region of the c-myc oncogene, rendering the gene inactive, in a mutant line of mice. By looking for -- and not finding -- the specific translocation in these mice, he showed that c-myc had to be active in order for its DNA break to take place.

He then inserted a DNA tag into the mouse genome that allowed him to induce a break at the c-myc gene, which occurs only very rarely if left to its own devices. He found that his artificially created breaks were comparable in most every way to the breaks caused by AID, but when he looked for the translocation in mice that didn’t produce this enzyme, they were nowhere to be found.

“This is a definitive study,” says Nussenzweig, who is also a Howard Hughes Medical Institute investigator. “We now know AID is causing damage in other parts of the genome, not just in antibody genes.”

Because AID normally enables the genetic experimentation that’s critical to an effective immune response, shutting it down even to fight cancer is perilous. “As a general rule, you wouldn’t want to give an AID inhibitor to everyone because immune systems would not be working so well,” Nussenzweig says. Still, a pharmaceutical AID inhibitor, if developed, might prove useful in treating certain tumors that are expressions of this powerful gene mutator.

The next step is to figure out exactly how AID works and identify other genetic sites where AID is active. “We are now developing the tools to do exactly that,” Robbiani says.

Brett Norman | Newswise Science News
Further information:
http://www.rockefeller.edu

More articles from Life Sciences:

nachricht For a chimpanzee, one good turn deserves another
27.06.2017 | Max-Planck-Institut für Mathematik in den Naturwissenschaften (MPIMIS)

nachricht New method to rapidly map the 'social networks' of proteins
27.06.2017 | Salk Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Touch Displays WAY-AX and WAY-DX by WayCon

27.06.2017 | Power and Electrical Engineering

Drones that drive

27.06.2017 | Information Technology

Ultra-compact phase modulators based on graphene plasmons

27.06.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>