Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

U-M researchers find key interaction that controls telomeres

17.02.2010
Finding could be basis for developing new cancer therapies

In the dominoes that make up human cells, researchers at the University of Michigan Comprehensive Cancer Center have traced another step of the process that stops cells from becoming cancerous.

It starts with the enzyme telomerase, which affects the caps, or telomeres, at the end of a chromosome. Telomeres shorten over time. But telomerase prevents this from happening, making the cell immortal. If cancer is triggered in the cell, the presence of telomerase leads to the growth of the cancer.

Telomerase is kept in control by the protein TRF1, which keeps the telomeres operating correctly. But another protein, Fbx4, can bind to TRF1 and degrade it, causing the telomeres to lengthen.

Now, researchers have discovered, a third protein, TIN2, can step in and override Fbx4 by binding to TRF1 first and preventing Fbx4 from attaching to it.

This finding paves the way for developing a drug that acts like TIN2, keeping everything in check and stopping the first domino from falling.

Results of the study appear in the Feb. 16 issue of Developmental Cell.

“In 90 percent of cancers, no matter what caused the cancer to form, it needs telomerase activity to maintain the cell. Without telomerase, the cell will die. Our work is key to understanding a detailed mechanism for how these molecules interact and how to design a drug to block Fbx4,” says senior author Ming Lei, Ph.D., assistant professor of biological chemistry at the University of Michigan Medical School.

The researchers found that the location in the molecule where Fbx4 binds to TRF1 overlaps with where TIN2 binds to TRF1. Where both Fbx4 and TIN2 are present, the TIN2 wins out and binds to the TRF1 first. This blocks Fbx4 from binding to the TRF1, thereby stabilizing TRF1 and keeping the telomere length in control.

The researchers are now looking at peptides that mimic TIN2’s binding to TRF1, in order to block Fbx4. The work is still in preliminary stages and no new therapies are being tested in patients.

If a drug is discovered, it could impact all cancer types. Currently, molecularly targeted therapies address a pathway or gene that’s involved in only specific types of cancer. But telomerase is involved in all types of cancer.

“If we find a drug that can inhibit telomerase activity in any fashion, that could be a universal cancer drug,” says Lei, a Howard Hughes Medical Institute Early Career Scientist.

Additional authors: Zhixiong Zeng, Wei Wang, Yuting Yang, Yong Chen, Xiaomei Yang, J. Alan Diehl, and Xuedong Liu

Funding: National Institutes of Health, American Cancer Society Research Scholar grant, Sidney Kimmel Scholar Award, National Cancer Institute, National Institute of General Medical Science, and the U.S. Department of Energy’s Office of Basic Energy Sciences

Reference: Developmental Cell, Vol. 18, No. 2, pp. 214-225

Nicole Fawcett | EurekAlert!
Further information:
http://www.umich.edu

More articles from Life Sciences:

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

nachricht Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Underwater acoustic localization of marine mammals and vehicles

23.11.2017 | Information Technology

Enhancing the quantum sensing capabilities of diamond

23.11.2017 | Physics and Astronomy

Meadows beat out shrubs when it comes to storing carbon

23.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>