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 Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University

nachricht How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung

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 the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>