Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UT Southwestern researchers discover master switch in cell death

01.07.2005


Researchers at UT Southwestern Medical Center have found an enzyme vital for controlling the early stages of cell death - a beneficial and normal process when it works right, but malignant in a variety of cancers when it malfunctions.



The researchers are now examining tissue from cancer patients to try to determine how mutations in the enzyme’s gene may relate to cancer. "We think this gene will really be a hot spot in research," said Dr. Qing Zhong, postdoctoral researcher in biochemistry at UT Southwestern and lead author of a paper to be published in the July 1 issue of the journal Cell.

The life and death of cells is a complex avalanche of reactions, controlled by a few molecules that sit atop a biochemical "pyramid."


The newly discovered enzyme, which the researchers have named Mule, destroys a key molecule at the top of the pyramid, thus leading to the cascading disintegration of the cell. Their findings also suggest a new drug target for controlling tumor formation.

Dr. Xiaodong Wang, professor of biochemistry at UT Southwestern and a researcher with the Howard Hughes Medical Institute, said the discovery of Mule will open up a whole field of research to study the enzyme’s role in normal cell death and cancer.

"We think these findings are very significant," said Dr. Wang, senior author of the Cell study. "This is the first enzymatic step that regulates the degradation of proteins that control cell death."

The beneficial side of cell death - known as apoptosis - occurs when it kills cells at appropriate times, as is the case, for example, when it removes the webbing from the fingers of an embryo or shapes a developing brain. But the darker side of this complex process manifests itself in cancers when cells don’t die when they’re supposed to.

The key to the researchers’ finding was the interaction between the Mule enzyme and a major player in cell death, the protein Mcl-1. Dr. Wang said that while there are many possible routes a cell may take toward apoptosis, this interaction serves as one of the "master switches" controlling whether or not those other pathways are triggered.

Normally, Mcl-1 keeps cells alive by protecting them against apoptosis. For a cell to die, Mcl-1 has to be disabled. "It’s just like a guardian," Dr. Zhong said.

A healthy organism needs just the right amount of Mcl-1. Too little Mcl-1 can lead to a damaged immune system or even death. Too much, and cells stay alive when they shouldn’t, leading to cancers such as lymphomas.

Using human cell extracts, the researchers found that Mule caused a protein called ubiquitin to bind to several sites on Mcl-1. When ubiquitin binds to a molecule, it serves as a flag for that molecule to be destroyed.

"If you have too much Mule in a cell, Mcl-1 will degrade tremendously," Dr. Zhong said.

The search for Mule took more than two years, as the UT Southwestern researchers specifically searched for an enzyme that controls Mcl-1.

The interaction between Mule and Mcl-1 might someday be manipulated to help cancer patients, Dr. Wang said. For instance, a tumor may contain cells with a deficit of Mule, making the tumor more likely to grow and perhaps be resistant to chemotherapy. Treatment might then focus on the biochemistry of Mule and Mcl-1, he said.

"We might be able to see if there’s a problem with Mule, or perhaps we could screen beforehand," Dr. Wang said.

Other UT Southwestern researchers involved in the study were Wenhua Gao, student research assistant, and Dr. Fenghe Du, research specialist.

The work was supported by the Howard Hughes Medical Institute, the National Institutes of Health and The Welch Foundation.

Aline McKenzie | EurekAlert!
Further information:
http://www.utsouthwestern.edu

More articles from Life Sciences:

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Researchers shoot for success with simulations of laser pulse-material interactions

29.03.2017 | Materials Sciences

Igniting a solar flare in the corona with lower-atmosphere kindling

29.03.2017 | Physics and Astronomy

As sea level rises, much of Honolulu and Waikiki vulnerable to groundwater inundation

29.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>