Corporate Banner
Satellite Banner
Biomolecular Screening
Scientific Community
 
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
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 2,500+ scientific posters on ePosters
  • More than 3,700+ 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

Simple Technology Makes CRISPR Gene Editing Cheaper
University of California, Berkeley, researchers have discovered a much cheaper and easier way to target a hot new gene editing tool, CRISPR-Cas9, to cut or label DNA.
Friday, July 24, 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
Engineers Crack DNA Code of Autoimmune Disorders
Researchers have identified an unexpectedly general set of rules that determine which molecules can cause the immune system to become vulnerable to the autoimmune disorders lupus and psoriasis.
Wednesday, June 10, 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
Industry-Sponsored Academic Inventions Spur Increased Innovation
Analysis questions assumption that corporate support skews science toward inventions that are less useful than those funded by the government or non-profit organizations.
Monday, March 24, 2014
Chemical Signature for Fast Form of Parkinson's Found
The physical decline experienced by Parkinson's disease patients eventually leads to disability and a lower quality of life.
Monday, November 25, 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
Discovery Could Lead to Saliva Test for Pancreatic Cancer
The disease is typically diagnosed through an invasive and complicated biopsy.
Tuesday, October 15, 2013
Biologists Find New Method for Discovering Antibiotics
Biologists have developed a revolutionary new method for identifying and characterizing antibiotics.
Tuesday, September 17, 2013
Potential Drug Discovered for Severe Form of Epilepsy
UCSF study found effectiveness of antihistamine on zebrafish bred to mimic disease.
Thursday, September 05, 2013
Potential New Drug for Inflammatory Bowel Disease
Vedolizumab, a new intravenous antibody medication, has shown positive results for treating both Crohn's disease and ulcerative colitis.
Monday, September 02, 2013
Dentistry School Receives $5M to Study Saliva Biomarkers
Imagine having a sample of your saliva taken at the dentist's office, and then learning within minutes whether your risk for stomach cancer is higher than normal.
Thursday, August 15, 2013
Brain Anomolies are Potential Biomarkers for Autism
Brain anomalies may serve as potential biomarkers for the early identification of the neurodevelopmental disorder.
Wednesday, July 10, 2013
Second Amyloid May Play a Role in Alzheimer's
The study is the first to identify deposits of the protein, called amylin, in the brains of people with Alzheimer's disease.
Monday, July 01, 2013
Scientific News
Promising Class of New Cancer Drugs Cause Memory Loss in Mice
New findings from The Rockefeller University suggest that the original version of BET inhibitors causes molecular changes in mouse neurons, and can lead to memory loss in mice that receive it.
Electrical Control of Cancer Cells
Research led by scientists at The University of Texas Health Science Center at Houston (UTHealth) has revealed a new electrical mechanism that can control these switches.
Signature of Microbiomes Linked to Schizophrenia
Studying microbiomes in throat may help identify causes and treatments of brain disorder.
Inflammation Linked to Colon Cancer Metastasis
A new Arizona State University research study led by Biodesign Institute executive director Raymond DuBois has identified for the first time the details of how inflammation triggers colon cancer cells to spread to other organs, or metastasize.
Structural Discoveries Could Aid in Better Drug Design
Scientists have uncovered the structural details of how some proteins interact to turn two different signals into a single integrated output.
Determining the Age of Fingerprints
Watch the imprint of a tire track in soft mud, and it will slowly blur, the ridges of the pattern gradually flowing into the valleys. Researchers have tested the theory that a similar effect could be used to give forensic scientists a way to date fingerprints.
Genetic Overlapping in Multiple Autoimmune Diseases May Suggest Common Therapies
CHOP genomics expert leads analysis of genetic architecture, with eye on repurposing existing drugs.
Surprising Mechanism Behind Antibiotic-Resistant Bacteria Uncovered
Now, scientists at TSRI have discovered that the important human pathogen Staphylococcus aureus, develops resistance to this drug by “switching on” a previously uncharacterized set of genes.
Tissue Bank Pays Dividends for Brain Cancer Research
Checking what’s in the bank – the Brisbane Breast Bank, that is – has paid dividends for UQ cancer researchers.
Researchers Publish Landmark “Basket Study”
Researchers from Memorial Sloan Kettering Cancer Center (MSK) have announced results from the first published basket study, a new form of clinical trial design that explores responses to drugs based on the specific mutations in patients’ tumors rather than where their cancer originated.
SELECTBIO

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
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!