Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Balancing act at chromosome ends

01.04.2005


Scientists identify novel regulator of telomere homeostasis



Each of our 46 chromosomes is capped by a telomere – a long stretch of repeated DNA (TTAGG). Telomeres play a key protective function in our cells, and now Dr. In Kwon Chung and colleagues at Yonsei University (Seoul, Korea) and the University of Central Florida reveal a novel mechanism to modulate telomere length. Their work will be published in the April 1st issue of Genes & Development.

With each round of cell division, telomeres are progressively shortened. In fact, when telomeres reach a "critical length" the cell can no longer multiply. This has lead many scientists to conclude that the erosion of telomeres is a key feature of the aging process, while the aberrant addition to telomere ends (and increased proliferative capacity that this endows) is an integral part of cancer progression.


The mechanisms by which a cell regulates activity at its telomeres (be it positive or negative), is an actively investigated area, with direct implications for understanding aging and cancer.

Telomeres are elongated by an enzyme called Telomerase (hTERT). Telomerase is generally only active in fetal, germ, and cancer cells; it is normally repressed in most somatic (body) cells. This new work by Dr. Chung and colleagues shows how cells keep telomerase activity in check, by identifying a novel protein that tags its key partner for degradation.

Hsp90 is an abundant cellular protein that specifically interacts with hTERT to promote telomere formation. The Hsp90 protein is increased in several tumors and may increase the addition of telomere repeats several-fold. Chung’s group has now identified a second protein, called MKRN1 that acts on hTERT to promote its degradation. MKRN1 belongs to a class of proteins called ubiquitin ligases that catalyze the addition of a small protein, called ubiquitin, to mark hTERT for destruction by cellular degradation machinery.

Increasing the amount of MKRN1 in cells promotes the degradation of hTERT and leads to a decreased telomerase activity. This degradation is even more pronounced in cells that are treated with the drug geldanamycin, which is a specific antagonist of Hsp90. Consequently, this causes the shortening of telomere lengths. Using biochemical assays, it was demonstrated that MKRN1 directly interacts with hTERT to promote the addition of the ubiquitin moieties.

These results indicate that two opposing forces in human cells influence basal levels of active hTERT. The first is an interaction with Hsp90 that promotes this activity and the other is protein degradation, mediated by MKRN1 and the balance of these two maintains cellular telomerase levels. The identification of MKRN1 as a negative regulator of telomere lengths is an important finding in elucidating how cells may achieve immortality to lead to cancers.

Further studies will be important to shed light on how MKRN1 may be used as a therapeutic target for checking the uncontrolled division of tumor cells. Dr. Chung is confident that "MKRN1 plays an important role in modulating telomere homeostasis through dynamic control of hTERT protein stability and could represent a novel target for anti-cancer drug development."

Heather Cosel | EurekAlert!
Further information:
http://www.cshl.edu

More articles from Life Sciences:

nachricht Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University

nachricht Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017
25.04.2017 | Laser Zentrum Hannover e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

NASA's Fermi catches gamma-ray flashes from tropical storms

25.04.2017 | Physics and Astronomy

Researchers invent process to make sustainable rubber, plastics

25.04.2017 | Materials Sciences

Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017

25.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>