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 Clock stars: Astrocytes keep time for brain, behavior
27.03.2017 | Washington University in St. Louis

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Electrical 'switch' in brain's capillary network monitors activity and controls blood flow

27.03.2017 | Health and Medicine

Clock stars: Astrocytes keep time for brain, behavior

27.03.2017 | Life Sciences

Sun's impact on climate change quantified for first time

27.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>