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 How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>