Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein identified as enemy of vital tumor suppressor PTEN

04.05.2011
UT MD Anderson-led team finds evidence that WWP2 subverts a brake on cell growth

A protein known as WWP2 appears to play a key role in tumor survival, a research team headed by a scientist at The University of Texas MD Anderson Cancer Center reports in an advance online publication of Nature Cell Biology.

Their research suggests that the little-studied protein binds to the tumor-suppressing protein PTEN (phosphatase and tensin homologue deleted on chromosome 10), marking it for destruction by proteasomes, which degrade proteins and recycle their components.

PTEN plays a role regulating the cellular reproduction cycle and prevents rapid cell growth, a hallmark of malignant cells. Its gene is mutated or deleted in many types of cancer, the researchers noted.

The WWP2 (atrophin-1 interacting protein 2) protein was discovered in the laboratory of Junjie Chen, Ph.D., professor and chair in MD Anderson's Department of Experimental Radiation Oncology and senior author of the paper.

"We were trying to find regulators of PTEN when we isolated the protein WWP2 as a putative PTEN-associated protein," Chen said. He noted that WWP2 caught the researchers' attention because it is similar to the NEDD4-1 protein, which has been proposed as a regulator of PTEN function.

First suspect doesn't affect PTEN

WWP2 is an E3 ubiquitin ligase in the NEDD4-like protein family. Ubiquitins attach to other proteins, labeling them for degradation by proteasomes. NEDD4-like proteins play important roles regulating gene transcription, embryonic stem cells, cellular transport and activation of T cells.

"But when NEDD4-1 is deleted in mice, researchers have not seen a clear change in PTEN protein level," Chen noted. "These findings suggest that there may be other PTEN regulators.

"Because WWP2 is part of the NEDD4-like family, we decided to take a look at it to see if it's the real regulator of PTEN," Chen continued. "When you knock down WWP2, you see an increase in PTEN level, whereas with WWP2 overexpression you can see a decrease in PTEN. This finding indicates that WWP2 may be involved in PTEN's regulation."

Overall, the study results suggest that WWP2 can regulate PTEN stability, Chen said.

Possibly a cancer-driving gene

The team uncovered evidence that WWP2 is a potential oncogene - a driver in tumor formation and growth. In one experiment, mice with normal WWP2 developed prostate cancer tumors after nine weeks that were more than three times the size of tumors in mice with WWP2 silenced.

Chen noted that more research is needed to determine whether WWP2 is functionally important in tumors or in tumor formation. "We need to look at real tumor samples to determine whether tumors with reduced PTEN expression could result from the overexpression of WWP2."

He added that some early studies suggest that WWP2 may operate in tumors, but a correlation between WWP2 overexpression and PTEN downregulation in tumors has not been established.

This work was supported in part by a grant from the Department of Biotechnology, Ministry of Science and Technology, India, a U.S. Department of Defense Era of Hope Research Scholar Award, an NIH Specialized Program of Research Excellence award to Mayo Clinic, and a National Cancer Institute grant to MD Anderson. Also, fellowship support came from the Department of Biotechnology, Council of Scientific and Industrial Research and University Grants Commission, India, and support from the Institute of Life Sciences, Hyderabad, India.

Co-authors with Chen are first author Subbareddy Maddika, Ph.D, Sridhar Kavela, Neelam Rani, and Vivek Reddy Palicharla, all of the Laboratory of Cell Death and Cell Survival, Centre for DNA Fingerprinting and Diagnostics in Nampally, Hyderabad, India; Jenny Pokorny and Jann Sarkaria, M.D., of the Mayo Clinic, Rochester, Minn.

About MD Anderson

The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. MD Anderson is one of only 40 comprehensive cancer centers designated by the National Cancer Institute. For seven of the past nine years, MD Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News & World Report.

Scott Merville | EurekAlert!
Further information:
http://www.mdanderson.org

More articles from Life Sciences:

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>