Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Scientists Map Cancer-, Aging-Related Enzyme

Published: Friday, April 12, 2013
Last Updated: Friday, April 12, 2013
Bookmark and Share
Researchers have solved the puzzle of how the various components of an entire telomerase enzyme complex fit together and function in a three-dimensional structure.

The creation of the first complete visual map of the telomerase enzyme, which is known to play a significant role in aging and most cancers, represents a breakthrough that could open up a host of new approaches to fighting disease, the researchers said.

"Everyone in the field wants to know what telomerase looks like, and there it was. I was so excited, I could hardly breathe," said Juli Feigon, a UCLA professor of chemistry and biochemistry and a senior author of the study. "We were the first to see it."

The scientists report the positions of each component of the enzyme relative to one another and the complete organization of the enzyme's active site. In addition, they demonstrate how the different components contribute to the enzyme's activity, uniquely correlating structure with biochemical function.

The research appears today (April 11) in the print edition of the journal Nature and is available online.
"We combined every single possible method we could get our hands on to solve this structure and used cutting-edge technological advances," said co-first author Jiansen Jiang, a researcher who works with Feigon and the study's co-senior author, Z. Hong Zhou, director of the Electron Imaging Center for Nanomachines at the California NanoSystems Institute at UCLA and a professor of microbiology, immunology and molecular genetics. "This breakthrough would not have been possible five years ago."

"We really had to figure out how everything fit together, like a puzzle," said co-first author Edward Miracco, a National Institutes of Health postdoctoral fellow in Feigon's laboratory. "When we started fitting in the high-resolution structures to the blob that emerged from electron microscopy, we realized that everything was fitting in and made sense with decades of past biochemistry research. The project just blossomed, and the blob became a masterpiece."

The telomerase enzyme is a mixture of components that unite inside our cells to maintain the protective regions at the ends of our chromosomes, which are called telomeres. Telomeres act like the plastic tips at the end of shoelaces, safeguarding important genetic information. But each time a cell divides, these telomeres shorten, like the slow-burning fuse of a time bomb. Eventually, the telomeres erode to a point that is no longer tolerable for cells, triggering the cell death that is a normal part of the aging process.

While most cells have relatively low levels of telomerase, 80 percent to 90 percent of cancer cells have abnormally high telomerase activity. This prevents telomeres from shortening and extends the life of these tumorigenic cells — a significant contributor to cancer progression.

The new discovery creates tremendous potential for pharmaceutical development that takes into account the way a drug and target molecule might interact, given the shape and chemistry of each component. Until now, designing a cancer-fighting drug that targeted telomerase was much like shooting an arrow to hit a bull's-eye while wearing a blindfold. With this complete visual map, the researchers are starting to remove that blindfold.

"Inhibiting telomerase won't hurt most healthy cells but is predicted to slow down the progression of a broad range of cancers," said Miracco. "Our structure can be used to guide targeted drug development to inhibit telomerase, and the model system we used may also be useful to screen candidate drugs for cancer therapy."

The researchers solved the structure of telomerase in Tetrahymena thermophila, the single-celled eukaryotic organism in which scientists first identified telomerase and telomeres, leading to the 2009 Nobel Prize in medicine or physiology. Research on Tetrahymena telomerase in the lab of co-senior author Kathleen Collins, a professor of molecular and cell biology at UC Berkeley, laid the genetic and biochemical groundwork for the structure to be solved.

"The success of this project was absolutely dependent on the collaboration among our research groups," said Feigon.

"At every step of this project, there were difficulties," she added. "We had so many technical hurdles to overcome, both in the electron microscopy and the biochemistry. Pretty much every problem we could have, we had, and yet at each stage these hurdles were overcome in an innovative way."

One of the biggest surprises, the researchers said, was the role of the protein p50, which acts as a hinge in Tetrahymena telomerase to allow dynamic movement within the complex; p50 was found to be an essential player in the enzyme's activity and in the recruitment of other proteins to join the complex.

"The beauty of this structure is that it opens up a whole new world of questions for us to answer," Feigon said. "The exact mechanism of how this complex interacts with the telomere is an active area of future research."

"The atmosphere and collaboration at UCLA really amazes me, and that is combined with some of the most advanced facilities around," Zhou said. "We have a highly advanced electron microscopy facility here at UCLA that even researchers without a strong background in electron microscopy can learn how to use and benefit from. This will be really useful as we move forward."

This research was funded by the National Science Foundation and the National Institutes of Health. Equal contributions to the publication were made by co-first authors Jiang and Miracco, postdoctoral researchers at UCLA with Zhou and Feigon. Members of Kathleen Collins' UC Berkeley laboratory who contributed to this research included technician Kyungah Hong, postdoctoral researcher Barbara Eckert and former graduate researcher Bosun Min. Other co-authors included Henry Chan and Darian D. Cash, UCLA graduate student researchers in Feigon's laboratory.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,200+ scientific posters on ePosters
  • More Than 4,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

‘Human-on-a-Chip’ Could Replace Animal Testing
Researchers are developing a “human-on-a-chip,” a miniature external replication of the human body, integrating biology and engineering with a combination of microfluidics and multi-electrode arrays.
Monday, June 13, 2016
Unveiling the Complexity of Mysterious Protein Folding
Imagine trying to reverse engineer a car when all you have is a finished product or a box full of parts — no instructions.
Wednesday, June 01, 2016
Study Identifies How Brain Connects Memories Across Time
UCLA Neuroscientists have boost ability of aging brain to recapture links between related memories.
Tuesday, May 31, 2016
Transcription Factor Isoforms Implicated in Colon Diseases
UC Riverside study explains how distribution of two forms of a transcription factor in the colon influence risk of disease.
Thursday, May 19, 2016
An E.coli Detector May be in Your Hands Soon
Hand-held device that can be used to detect a variety of pathogens—including foodborne pathogens like E. coli—at all stages in the food supply chain, from fields to restaurants may be available soon.
Monday, May 16, 2016
Fructose Alters Hundreds of Brain Genes
UCLA scientists report that diet rich in omega-3 fatty acids can reverse the damage.
Tuesday, April 26, 2016
Study Yields the Key to Effective Personalized Medicine
A team of UCLA bioengineers and surgeons has taken a major step toward making personalized medicine a reality.
Monday, April 11, 2016
Tracking RNA in Live Cells
Technique may open doors to new treatments for many conditions, from cancer to autism.
Friday, March 18, 2016
Cat Stem Cell Therapy Gives Humans Hope
By the time Bob the cat came to the UC Davis veterinary hospital, he had used up most of his nine lives.
Monday, February 08, 2016
Crowdfunding the Fight Against Cancer
From budding social causes to groundbreaking businesses to the next big band, crowdfunding has helped connect countless worthy projects with like-minded people willing to support their efforts, even in small ways. But could crowdfunding help fight cancer?
Monday, February 08, 2016
Toxic Pollutants Found in Fish Across the World's Oceans
Scripps researchers' analysis shows highly variable pollutant concentrations in fish meat.
Friday, January 29, 2016
Key Enzyme in Pierce’s Disease Grapevine Damage Uncovered
UC Davis plant scientists have identified an enzyme that appears to play a key role in the insect-transmitted bacterial infection of grapevines with Pierce’s disease, which annually costs California’s grape and wine industries more than $100 million.
Wednesday, January 13, 2016
Science Magazine Names CRISPR ‘Breakthrough of the Year’
In its year-end issue, the journal Science chose the CRISPR genome-editing technology invented at UC Berkeley 2015’s Breakthrough of the Year.
Monday, December 21, 2015
Genome Sequencing May Save California's Legendary Sugar Pine
The genome of California’s legendary sugar pine, which naturalist John Muir declared to be “king of the conifers” more than a century ago, has been sequenced by a research team led by UC Davis scientists.
Thursday, December 17, 2015
Cellular “ORACLs” to Aid Drug Discovery
New approach for finding therapeutics is inspired by face-recognition software.
Wednesday, December 16, 2015
Scientific News
Open Source Seed Initiative – A Welcome Boost to Global Crop Breeding
A team of plant breeders, farmers, non-profit agencies, seed advocates, and policymakers have created the Open Source Seed Initiative.
ASMS 2016: Targeting Mass Spectrometry Tools for the Masses
The expanding application range of MS in life sciences, food, energy, and health sciences research was highlighted at this year's ASMS meeting in San Antonio, Texas.
Implementation Science Approaches to Reduce Mother-to-Child HIV Transmission
The NIH study will investigate best practices to ease major disease burden in Sub-Saharan Africa.
Tough New Hydrogel Hybrid Doesn’t Dry Out
Water-based material could be used to make artificial skin, longer-lasting contact lenses.
New CAR T Cell Therapy Using Double Target Aimed at Solid Tumors
Researchers at Penn University have described how antibody, carbohydrate combination could apply to range of cancer types.
Lasers Carve the Path to Tissue Engineering
A new technique, developed at EPFL, combines microfluidics and lasers to guide cells in 3D space, overcoming major limitations to tissue engineering.
Link Between Canned Food, BPA Exposure Revealed
New Stanford research resolves the debate on the link between canned food and exposure to the hormone-disrupting chemical known as Bisphenol A, or BPA.
Portable Test Rapidly Detects Zika
To better diagnose and track the disease, scientists are now reporting a new $2 test that in the lab can accurately detect low levels of the virus in saliva.
Erasing Unpleasant Memories with a Genetic Switch
Researchers from KU Leuven and the Leibniz Institute for Neurobiology have managed to erase unpleasant memories in mice using a 'genetic switch'.
Unidentified Spectra Detector
New algorithm clusters over 250 million spectra for analysis, such that millions of unidentified peptide sequences can be recognised.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,200+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!