Microbiologists identify two molecules that kill lymphoma cells in mice

Nov 06, 2011

Researchers at the University of Southern California have identified two molecules that may be more effective cancer killers than are currently available on the market.

The , molecules derived from a cancer-causing virus, an enzyme in that regulates a widely researched known as p53. The peptides inhibit the enzyme, causing p53 levels in to rise, which leads to . Lymphoma tumors in mice injected with the two peptides showed marked regression with no significant weight-loss or gross abnormalities.

The discovery is detailed in the journal Nature Structural & Molecular Biology, which posts online on Sunday, Nov. 6.

HAUSP, or herpesvirus-associated ubiquitin specific protease, is an enzyme that cleaves the normally occurring protein ubiquitin from substrates like p53. In a healthy environment, ubiquitin binds to a substrate, causing it to degrade and die.

"Given the mounting evidence that HAUSP serves as a pivotal component regulating p53 protein levels, the inhibition of HAUSP should have the benefit to fully activate p53," said Hye-Ra Lee, Ph.D., the study's first author and a research fellow in the Department of Molecular Microbiology & Immunology at the Keck School of Medicine of USC.

Using co-crystal structural analysis, Lee and her colleagues found a tight, "belt-type" interaction between HAUSP and a viral protein that causes Kaposi's sarcoma and . The peptides derived from this viral protein bind 200 times more strongly to HAUSP than p53, making them ideal HAUSP inhibitors. The researchers found that the peptides comprehensively prevented HAUSP from cleaving ubiquitin, allowing p53 levels to rise — thereby representing potential new chemotherapeutic molecules that can be used for anti-cancer therapies.

New research is under way with Nouri Neamati, Ph.D., associate professor of pharmacology and pharmaceutical sciences
in the USC School of Pharmacy, to find small molecules that mimic the peptides. The peptides and other small molecules are being tested on different cancers.

"Significant advances in scientific understanding often come at the intersection of independent lines of research from different disciplines, for instance, structure and virus study. Time after time, viruses are teaching us," said Jae Jung, Ph.D., the study's principal investigator and chairman of the Department of Molecular Microbiology & Immunology at the Keck School of Medicine.

Explore further: Team develops 'cool' new method for probing how molecules fold

Related Stories

New drug shrinks cancer in animals, study shows

Apr 06, 2011

A study led by researchers at the University of Michigan Comprehensive Cancer Center showed in animal studies that new cancer drug compounds they developed shrank tumors, with few side effects.

Cancer is a p53 protein aggregation disease

Mar 29, 2011

Protein aggregation, generally associated with Alzheimer's and mad cow disease, turns out to play a significant role in cancer. In a paper published in Nature Chemical Biology, Frederic Rousseau and Joost Schymkowitz of VIB ...

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."

Recommended for you

'Hairclip' protein mechanism explained

13 hours ago

Research led by the Teichmann group on the Wellcome Genome Campus has identified a fundamental mechanism for controlling protein function. Published in the journal Science, the discovery has wide-ranging implications for bi ...

Discovery in the fight against antibiotic-resistant bacteria

15 hours ago

For four years, researchers at Universite catholique de Louvain have been trying to find out how bacteria can withstand antibiotics, so as to be able to attack them more effectively. These researchers now understand how one ...

Stem cells born out of indecision

15 hours ago

Scientists at the University of Copenhagen have gained new insight into embryonic stem cells and how blocking their ability to make choices explains why they stay as stem cells in culture. The results have just been published ...

User comments : 2

Adjust slider to filter visible comments by rank

Display comments: newest first

GMRoper
not rated yet Nov 07, 2011
Having been recently diagnosed with non-Hodgkin's Lymphoma, this can't come fast enough.
annie86
not rated yet Nov 08, 2011
I am sorry but, I don't understand this article. if HAUSP is inhibited, p53 will be degenerated faster due to its binding with ubiquitin, then how its level raises due to this article?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.