Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stanford scientists identify key component in cell replication

02.02.2009
Last week, a presidential limousine shuttled Barack Obama to the most important job in his life.

Scientists at the Stanford University School of Medicine have now identified a protein that does much the same for the telomerase enzyme — ferrying the critically important clump of proteins around to repair the ends of chromosomes that are lost during normal replication. Without such ongoing maintenance, stem cells would soon cease dividing and embryos would fail to develop.

"This is the first new protein component of telomerase that has been identified in 10 years," said Steven Artandi, MD, PhD, associate professor of hematology. "And it's likely to be a valuable target for anti-cancer therapies."

Artandi is the senior author of the research, which will be published in the Jan. 30 issue of Science. Graduate student Andrew Venteicher is the first author. The two collaborated with scientists at the National Cancer Institute-Frederick and the University of Georgia to conduct the research.

Telomerase is normally expressed in adult stem cells and immune cells, as well as in cells of the developing embryo. In these cells, the enzyme caps off the ends of newly replicated chromosomes, allowing unfettered cell division. Without telomerase, cells stop dividing or die within a limited number of generations. Unfortunately, the enzyme is also active in many cancer cells. Artandi and his collaborators found that blocking the inappropriate expression of the protein, called TCAB1, in human cancer cells keeps telomerase from reaching its DNA targets, called telomeres, and may limit the cell's life span.

"There are currently no effective telomerase inhibitors," said Artandi. "We've never really understood before how the enzyme gets to the telomeres; it's been a complete black box. Now we're starting to piece together how it happens, and that gives us more opportunities to interfere with its function."

Telomerase has been subject of intense research for years, but scientists have been stymied by the enzyme's large size and extreme rarity. Few cells in the adult body make the huge protein complex, and even they make only tiny amounts. As a result, only some members have been identified.

"It's been incredibly challenging to figure out all the protein components of telomerase," said Artandi, who refers to the unknown members of the complex as "dark matter." "We know how big the enzyme is, and it's clear that the known components don't add up to the total. Now we've identified one more member."

The researchers used a highly sensitive protein identification technique called mass spectrometry to ferret out TCAB1's presence in telomerase based on its ability to bind to another, known component of the enzyme. Early last year, Artandi's lab used the same technique to identify for the first time two other proteins — pontin and reptin — that are important for assembling the massive complex. This time around they identified TCAB1, a protein of previously unknown function.

Unlike pontin and reptin, TCAB1 is a true component of telomerase. But it's not required for the enzyme's activity. Rather, it recruits the telomerase complex to processing and holding areas in the nucleus of the cell called Cajal (pronounced "cuh-hall") bodies. Like a high-end garage, Cajal bodies apply the finishing touches to a variety of proteins that use small molecules of RNA to conduct their activities (telomerase, for example, uses an RNA molecule as a template for the DNA chain it tacks onto the ends of chromosomes). When appropriate, TCAB1 then chauffeurs the telomerase complex to the waiting end of a newly replicated chromosome.

"TCAB1 is absolutely necessary for the telomerase to make this jump from Cajal bodies to telomeres," said Artandi. "When we inhibited its activity in human cancer cells, the telomeres grew shorter," implying the cancer cells would die more quickly.

Prior to this study, TCAB1 had no known function. "Andy [Venteicher] found that TCAB1 binds not only telomerase, but also a specific class of small, non-coding RNA molecules that also end up in the Cajal bodies," said Artandi. He added that the protein may be a common biological shuttle responsible for delivering a variety of molecules to their destinations. He and his collaborators plan to continue their study of TCAB1 and also to identify other telomerase components.

"This is a story that's been unfolding over decades," said Artandi. "Telomerase is such a high-priority target for many diseases, but it's hard to attack when you know very little about it. But that's changing now."

Krista Conger | EurekAlert!
Further information:
http://www.stanford.edu
http://mednews.stanford.edu

More articles from Life Sciences:

nachricht Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

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

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>