Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scripps Research Institute Scientists Uncover New Details of Natural Anticancer Mechanism

12.06.2013
Scientists at The Scripps Research Institute (TSRI) have identified key triggers of an important cancer-blocking mechanism in cells.
Termed “oncogene-induced senescence,” this mechanism can block most cancer types, and is commonly experienced when incipient skin cancers turn instead into slow-growing moles. Tumors that achieve malignancy often do so by defeating or circumventing this growth barrier—which is why scientists have been eager to find out precisely how it works.

“We have known about some of the molecular signals that mediate this senescence response, but we’ve needed to understand the signaling pathway in much more detail,” said Peiqing Sun, associate professor in TSRI’s Department of Cell and Molecular Biology.

In the new study, published recently by the journal Molecular Cell, Sun and his colleagues describe the cascading interactions of three enzymes that are necessary to initiate a common type of oncogene-induced senescence.

Looking for Binding Partners

Oncogenes are growth-related genes that, through DNA damage, inherited mutations or some other cause, push cells to keep dividing beyond normal limits. Oncogenes in the ras gene family are the ones that have been most commonly linked to human cancers—and most studied as triggers of senescence.

Sun and other researchers showed a decade ago that an enzyme called p38 sits near the top of the ras-induced senescence response cascade. In 2007, Sun and his colleagues reported that p38 plays a role in this cascade by activating another enzyme, PRAK, through the addition of a phosphor group, a modification known as phosphorylation. For the new study, Sun and first author Research Associate Hui Zheng, along with other members of the laboratory, sought more details of PRAK’s role in this cascade.

Zheng began the investigation by searching for binding partners of PRAK. With a series of protein-interaction assays he isolated an enzyme called Tip60, which binds tightly to PRAK. Further tests indicated that Tip60 does indeed lie within the senescence-inducing signaling cascade, because senescence fails to occur when Tip60 is absent.

PRAK is a kinase enzyme that, like p38, phosphorylates other proteins. Initially Zheng and Sun suspected that PRAK interacts with Tip60 by phosphorylating it, and thereby activating it.

Instead, the reverse turned out to be true: Tip60 acts on PRAK. Tip60 is a type of enzyme called an acetyltransferase, which modifies other proteins by adding acetyl groups. “Our tests showed that Tip60 binds to PRAK and acetylates it at a certain location, which helps activate PRAK,” said Zheng.

Thus, the key enzyme PRAK requires two signals: “First the phosphorylation by p38 and then the acetylation by Tip60 are required for fully activating PRAK in this senescence–induction cascade,” Zheng said.

Potential Cancer-Drug Strategy

What controls Tip60’s own activation in this cascade? None other than the master switch, p38. “As a first step, p38 phosphorylates both Tip60 and PRAK,” said Sun. Activated Tip60 then acetylates PRAK, completing PRAK’s activation.

Previously Sun and his laboratory have shown that PRAK, when activated, goes on to activate the key tumor-suppressor protein p53, which exerts more direct control over a cell’s growth machinery.

Sun and his team have been looking for ways to force the activation of the senescence response in cancer cells, as a potential cancer-drug strategy. “Finding these details of the early part of the signaling cascade helps us understand better what we need to target,” he said.

Other contributors to the study, “A Posttranslational Modification Cascade Involving p38, Tip60 and PRAK Mediates Oncogene-Induced Senescence,” were John Tat and Rong Liao of Sun’s laboratory, and Xuemei Han, Aaron Aslanian and John R. Yates III of the Yates lab at TSRI. For more information, see http://www.cell.com/molecular-cell/abstract/S1097-2765(13)00294-3

The study was funded in part by the National Institutes of Health (grants CA106768 and CA131231).

About The Scripps Research Institute

The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including three Nobel laureates—work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.
For information:
Office of Communications
Tel: 858-784-2666
Fax: 858-784-8136
press@scripps.edu

Mika Ono | EurekAlert!
Further information:
http://www.scripps.edu

More articles from Life Sciences:

nachricht Individual Receptors Caught at Work
19.10.2017 | Julius-Maximilians-Universität Würzburg

nachricht Rapid environmental change makes species more vulnerable to extinction
19.10.2017 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Rapid environmental change makes species more vulnerable to extinction

19.10.2017 | Life Sciences

Integrated lab-on-a-chip uses smartphone to quickly detect multiple pathogens

19.10.2017 | Interdisciplinary Research

Fossil coral reefs show sea level rose in bursts during last warming

19.10.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>