Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers pinpoint a new enemy for tumor-suppressor p53

30.06.2009
Researchers at The University of Texas M. D. Anderson Cancer Center have identified a protein that marks the tumor suppressor p53 for destruction, providing a potential new avenue for restoring p53 in cancer cells.

The new protein, called Trim24, feeds p53 to a protein-shredding complex known as the proteasome by attaching targeting molecules called ubiquitins to the tumor suppressor, the team reported this week in the Proceedings of the National Academy of Sciences Online Early Edition.

"Targeting Trim24 may offer a therapeutic approach to restoring p53 and killing tumor cells," said senior author Michelle Barton, Ph.D., professor in M. D. Anderson's Department of Biochemistry and Molecular Biology.

The discovery is based on an unusual approach to studying p53, which normally forces potentially cancerous cells to kill themselves and is shut down or depleted in most human cancers. Studies of the p53 protein and gene tend to focus on cancer cell lines or tumors, where the dysfunction already is established, Barton said. "We wanted to purify p53 from normal cells to better understand the mechanisms that regulate it."

The team developed a strain of mice with a biochemical tag attached to every p53 protein expressed. After first assuring that the tagged p53 behaved like normal p53, the team then used the tag, or hook, to extract the protein. "We could then identify proteins that were attached to p53, interacting with it, through mass spectrometry," Barton said.

They found Trim24, a protein previously unassociated with p53 that is highly expressed in tumors and is a target of two known oncogenes in distinct forms of leukemia and thyroid cancer.

Subsequent experiments showed that decreased levels of Trim24 led to increased levels of p53 expression in the cell nucleus, and increasing Trim24 expression reduced p53 levels. Loss of Trim24 expression in a breast cancer cell line caused spontaneous programmed cell death - apoptosis. A similar response was confirmed in human lung, colon and prostate cancer cells.

Treating cells with a proteasome inhibitor also led to increased p53 expression. Removing an important binding domain of Trim24 or depleting it completely both led to greatly reduced ubiquitin targeting of p53.

An analogous system in fruit flies showed that a simpler version of Trim24 in the flies plays a similar role regulating p53, demonstrating that the relationship is evolutionarily conserved.

Co-authors with Barton are first author Kendra Allton, Abhinav Jain, Ph.D., Hans-Martin Herz, Ph.D., Wen-Wei Tsai, Ph.D., Andres Bergmann, Ph.D., and Randy Johnson, Ph.D., all of M. D. Anderson's Department of Biochemistry and Molecular Biology; and Sung Yun Jung, Ph.D., and Jun Qin, Ph.D., of the Department of Molecular and Cellular Biology at Baylor College of Medicine. Allton completed the paper as her master's degree thesis for The University of Texas Graduate School of Biomedical Sciences, a joint program of M. D. Anderson and The University of Texas Health Science Center at Houston. Allton, Jain, Tsai, Johnson and Barton also are with M. D. Anderson's Center for Stem Cell and Developmental Biology.

Funding for the project was provided by M. D. Anderson's Kleberg Fund for Innovative Research, grants from the National Institutes of Health, CellCentric, Ltd., the Kadoorie Foundation, the Welch Foundation, the National Cancer Institute and the Laura and John Arnold Foundation Odyssey Fellowship (for Abhinav Jain).

About M. D. Anderson

The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 40 comprehensive cancer centers designated by the National Cancer Institute. For four of the past six years, including 2008, M. D. 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 Staying in Shape
16.08.2018 | Max-Planck-Institut für molekulare Zellbiologie und Genetik

nachricht Chips, light and coding moves the front line in beating bacteria
16.08.2018 | Okinawa Institute of Science and Technology (OIST) Graduate University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Staying in Shape

16.08.2018 | Life Sciences

Diving robots find Antarctic seas exhale surprising amounts of carbon dioxide in winter

16.08.2018 | Earth Sciences

Protein droplets keep neurons at the ready and immune system in balance

16.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>