Cell's fight against cancer revealed

Aug 31, 2006

If anything in cancer biology can be likened to a cage match, this is it: the battle inside the cell walls between LTag, "The Most Amazing Molecule in the Universe," and p53, "The Guardian of the Genome."

By the painstaking use of X-ray crystallography to track motion in very large molecules, a University of Southern California-led research group has taken a first look at the life-or-death struggle of a cancer-causing protein – LTag – and a key tumor suppressor – p53.

Each villainous LTag (short for large T antigen) single-handedly ties up a tag-team of six p53 molecules, inhibiting their tumor-suppressant role, the researchers report in the Sept. 1 issue of Genes & Development.

Undeterred, the p53 fight back by preventing replication of the virus that produces LTag, known as an oncoprotein for its function in cancer growth.

The champion depends on which side is stronger and healthier.

"If you have a lot of functional p53, you can override large T antigen," said lead researcher Xiaojiang Chen, professor in molecular and computational biology in the USC College of Letters, Arts and Sciences.

Sometimes called the "Guardian of the Genome," a damaged p53 can leave a cell almost defenseless.

"p53 is a very important tumor suppressor that's mutated in a vast majority of all cancers," said James Pipas, professor of biological sciences at the University of Pittsburgh.

It was Pipas who, after studying LTag for many years and marveling at its varied biological functions – including highly efficient tumor promotion – named it "The Most Amazing Molecule in the Universe" in one of his presentations.

Pipas called Chen's new study "a very important piece of work" that shows how a healthy cell's tumor defenses break down.

"Understanding exactly how this works is going to be a critical step toward our understanding of tumor genesis," he said.

This, in turn, may lead to new techniques for designing tumor-fighting drugs, Pipas added.

Chen's team was able to describe the interplay between LTag and p53 by crystallizing the complex of one LTag and six p53 molecules, totaling more than 50,000 atoms between them.

"It's quite a technical achievement, because these are fairly large proteins," Pipas said.

Chen said his study gave him new respect for LTag and its parent, Simian Virus 40. SV40 has long been used as a research tool to induce cancers in cell cultures.

"Somehow this virus knows how important p53 is, and has this oncoprotein (LTag) to target it by physically interacting with it and changing its conformation," Chen said.

If the virus succeeds, the result is a new tumor.

Source: University of Southern California

Explore further: Options for weight loss your primary care doctor might not know about

add to favorites email to friend print save as pdf

Related Stories

Evolutionary history of honeybees revealed by genomics

7 hours ago

In a study published in Nature Genetics, researchers from Uppsala University present the first global analysis of genome variation in honeybees. The findings show a surprisingly high level of genetic divers ...

Signatures of selection inscribed on poplar genomes

7 hours ago

One aspect of the climate change models researchers have been developing looks at how plant ranges might shift, and how factors such as temperature, water availability, and light levels might come into play. ...

Cutting emissions pays for itself, research shows

7 hours ago

Lower rates of asthma and other health problems are frequently cited as benefits of policies aimed at cutting carbon emissions from sources like power plants and vehicles, because these policies also lead ...

Recommended for you

Report advocates improved police training

9 hours ago

A new report released yesterday by the Mental Health Commission of Canada identifies ways to improve the mental health training and education that police personnel receive.

Discovery could lead to new cancer treatment

10 hours ago

A team of scientists from the University of Colorado School of Medicine has reported the breakthrough discovery of a process to expand production of stem cells used to treat cancer patients. These findings could have implications ...

User comments : 0