Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

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
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 2,700+ scientific posters on ePosters
  • More than 3,800+ 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 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

Opening the Door to Safer, More Precise Cancer Therapies
New method regulates when, and how strongly, cancer-killing therapeutic T cells are activated.
Tuesday, September 29, 2015
Scientists Create CRISPR/Cas9 Knock-In Mutations in Human T Cells
In a project spearheaded by investigators at UC San Francisco, scientists have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9.
Tuesday, July 28, 2015
Delivering Drugs to the Right Place
Thomas Weimbs has developed a targeted drug delivery method that could potentially slow the progression of polycystic kidney disease.
Monday, June 29, 2015
Designing New Pain Relief Drugs
Researchers have identified the molecular interactions that allow capsaicin to activate the body’s primary receptor for sensing heat and pain, paving the way for the design of more selective and effective drugs to relieve pain.
Thursday, June 11, 2015
Genetic Markers for Detecting and Treating Ovarian Cancer
Custom bioinformatics algorithm identifies human mRNAs that distinguish ovarian cancer cells from normal cells and provide new therapeutic targets
Wednesday, May 27, 2015
Using microRNA Fit to a T (Cell)
Researchers show B cells can deliver potentially therapeutic bits of modified RNA.
Friday, November 29, 2013
Digging Deeper Into Cancer
What a pathologist looks for in a Pap test sample, but hopes not to find, are oddly shaped cells with abnormally large nuclei. The same is true for prostate and lung cancer biopsies.
Tuesday, November 19, 2013
Nanotech Method Show Promise Against Pancreatic Cancer
Researchers at UCLA's Jonsson Comprehensive Cancer Center have developed a new technique for fighting deadly and hard-to-treat pancreatic cancer.
Monday, November 18, 2013
Researchers Un-Junking Junk DNA
A study shines a new light on molecular tools our cells use to govern regulated gene expression.
Wednesday, November 13, 2013
Powerful Anti-Cancer Compound Safely Delivered
Researchers have discovered a way to effectively deliver staurosporine (STS).
Tuesday, October 22, 2013
Pan-Cancer Studies Find Common Patterns Shared by Different Tumor Types
Findings may open up new treatment options by extending therapies effective in one cancer type to others with a similar genomic profile.
Wednesday, October 02, 2013
RNA Molecule Is Behind Behavior Changes Cued by Environment
UCSF study may point to key mechanism of cellular memory.
Thursday, September 05, 2013
Disabling Enzyme Cripples Tumors, Cancer Cells
Knocking out a single enzyme dramatically cripples the ability of aggressive cancer cells to spread and grow tumors.
Thursday, September 05, 2013
Scientists Devise Innovative Method to Profile and Predict the Behavior of Proteins
A class of proteins that are made up of multiple, interlocking molecular components, enzymes perform a variety of tasks inside each cell.
Friday, August 09, 2013
Non-Invasive Test Optimizes Colon Cancer Screening
Organized mailing campaigns could substantially increase colorectal cancer screening among uninsured patients.
Wednesday, August 07, 2013
Scientific News
Gene Editing Could Enable Pig-To-Human Organ Transplant
The largest number of simultaneous gene edits ever accomplished in the genome could help bridge the gap between organ transplant scarcity and the countless patients who need them.
Antioxidants Cause Malignant Melanoma to Metastasize Faster
Fresh research at Sahlgrenska Academy has found that antioxidants can double the rate of melanoma metastasis in mice.
Have Your Drug Nano-Delivered Via Microbubble
A UC engineering professor is working to develop effective nanoparticle-bubble drug delivery systems to access precise locations in the body to treat medical conditions such as cancer, eye disease and spinal disc degeneration.
Potential New Diagnosis and Therapy for Breast Cancer
Scientists at the University of York, using clinical specimens from charity Breast Cancer Now’s Tissue Bank, have conducted new research into a specific sodium channel that indicates the presence of cancer cells and affects tumour growth rates.
Paving the Way for Diamonds to Trace Early Cancers
Researchers from the University of Sydney reveal how nanoscale 'diamonds' can light up early-stage cancers in MRI scans.
Researchers Develop Classification Model for Cancers Caused by KRAS
Most frequently mutated cancer gene help oncologists choose more effective cancer therapies.
Tolerant Immune System Increases Cancer Risk
Researchers have found that individuals with high immunoCRIT ratios may have an increased risk of developing certain cancers.
Developing a Gel that Mimics Human Breast for Cancer Research
Scientists at the Universities of Manchester and Nottingham have been funded to develop a gel that will match many of the biological structures of human breast tissue, to advance cancer research and reduce animal testing.
New Gene Therapy for Vision Loss From a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
Predictive Model for Breast Cancer Progression
Biomedical engineers have demonstrated a proof-of-principle technique that could give women and their oncologists more personalized information to help them choose options for treating breast cancer.

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
2,700+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos