Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene that drives cells to commit suicide also plays key role in development of skeletal muscle

12.03.2003


St. Jude scientists say FKHR protein causes primitive cells called myoblasts to fuse, while deficiency of FKHR contributes to muscle cancer



Investigators at St. Jude Children’s Research Hospital have discovered that a protein causing mature cells to commit suicide also helps primitive muscle cells called myoblasts fuse together, allowing them to develop into muscles. The finding of this unexpected new role for the protein, called FKHR, suggests that future research might offer clues to how mutated forms of this molecule cause a form of muscle cancer in children called rhabdomyosarcoma.

Rhabdomyosarcoma is a highly malignant tumor arising when primitive cells called myoblasts do not fuse and differentiate into muscle, but rather grow uncontrollably. Rhabdomyosarcoma accounts for 5-8 percent of childhood cancers and is usually diagnosed within the first 10 years of life. The most aggressive form of rhabdomyosarcoma is the alveolar type, which usually affects muscles in the extremities or trunk. The other most common type, embryonal rhabdomyosarcoma, occurs in the head and neck region and genitourinary tract. The discovery of the role of FKHR is important because of the protein’s link to a childhood cancer. Mutations of the FKHR gene occur when a piece of either of two genes—PAX3 or PAX7—break away from their own chromosomes and attach to FKHR forming PAX3-FKHR or PAX7-FKHR “fusion genes.” These genes then cause rhabdomyosarcoma. Understanding the normal role of FKHR in myoblasts could help explain how the mutated FKHR genes cause cancer, according to the St. Jude researchers.


The study shows that FKHR not only has at least two different jobs, but also gets controlled in either of two different ways, depending on the context in which it works.

FKHR is a transcription factor, which regulates the activity of other specific genes, and in that way controls specific cellular processes.

“The fact that FKHR plays such vastly different roles depending on where it is, forces us to reassess the impact that a single transcription factor can have on cells,” said Gerard C. Grosveld, Ph.D., chairman of the St. Jude Department of Genetics. “It also alerts us to the possibility that a mutated transcription factor can have an unexpected role in a disease we’re already familiar with.” Grosveld is senior author of a report on these findings published in the March 3 issue of The EMBO Journal.

Using a variety of techniques in molecular biology, Grosveld and his co-author Philippe R. J. Bois, Ph.D., studied the movement of FKHR in the cell between the cytoplasm (main area of the cell) and the nucleus (compartment that holds the DNA) under varying conditions. They also studied the activation of genes by FKHR.

The St. Jude researchers found that as myoblasts multiply, most of the FKHR is found in the cytoplasm rather than the nucleus. That’s because the nucleus appears to continuously export the protein out of the nucleus and into the cytoplasm, according to Grosveld. But when a myoblast starts to differentiate, the rate at which FKHR is exported from the nucleus greatly decreases, as does the rate at which the cell breaks down this transcription factor. This causes the concentration of FKHR in the nucleus to rise. Differentiation is the process during which a primitive cell develops characteristics that make it a mature cell with a specific function.

“In the nucleus of the myoblast, FKHR binds to the DNA, where it activates genes that control the cell’s ability to fuse with other myoblasts and form muscles,” Grosveld said. “So it makes sense that raising the concentration of FKHR in the nucleus will permit this transcription factor to control the fusion process.” The St. Jude researchers found that FKHR is regulated by one process in most cells, but in a different way in myoblasts. In most cells, FKHR responds to hostile environments by stimulating a cascade of biochemical reactions that executes a process called programmed cell death, or apoptosis. But this activity is blocked when an enzyme called Akt attaches a phosphate molecule to each of three sites on FKHR. Phosphate is a molecule made up of a phosphorus atom and four oxygen atoms and is often used as a way to activate or inactivate various proteins that control signaling pathways in the cell.

However, in myoblasts undergoing differentiation, a different, unknown enzyme places phosphate molecules onto FKHR. This normally controls the activity of FKHR and the rate of myoblast fusion.

“It’s somewhat like pushing a button on a machine when it’s in different parts of the same factory, and seeing the machine respond in two different ways,” Grosveld said. “If you push the button when the machine is in one place, you stop the machine from doing a job you know it’s supposed to do. But if you push the button when the machine is in another part of the factory, it does a job you didn’t even know it could do.”

One of the most interesting observations the St. Jude researchers made is that when the level of FKHR in myoblasts is reduced, these cells no longer fuse. Grosveld and Bois propose that the reduced FKHR activity in the myoblasts contributes to their inability to fuse and helps these cells to become cancerous and cause rhabdomyosarcoma.


This work was supported in part by the National Cancer Institute, a cancer center (CORE) support grant and by ALSAC.

Philippe Bois is a fellow of the Van Vleet foundation in Memphis.

St. Jude Children’s Research Hospital
St. Jude Children’s Research Hospital, in Memphis, Tennessee, was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for catastrophic diseases of childhood. The hospital’s work is supported through funds raised by ALSAC. ALSAC covers all costs not covered by insurance for medical treatment rendered at St. Jude Children’s Research Hospital. Families without insurance are never asked to pay. For more information, please visit www.stjude.org.

Bonnie Cameron | EurekAlert!
Further information:
http://www.stjude.org/

More articles from Life Sciences:

nachricht New switch decides between genome repair and death of cells
27.09.2016 | University of Cologne - Universität zu Köln

nachricht A blue stoplight to prevent runaway photosynthesis
27.09.2016 | National Institute for Basic Biology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New welding process joins dissimilar sheets better

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of light metals.
Scientists at the University of Stuttgart have now developed two new process variants that will considerably expand the areas of application for friction stir welding.
Technologie-Lizenz-Büro (TLB) GmbH supports the University of Stuttgart in patenting and marketing its innovations.

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of...

Im Focus: First quantum photonic circuit with electrically driven light source

Optical quantum computers can revolutionize computer technology. A team of researchers led by scientists from Münster University and KIT now succeeded in putting a quantum optical experimental set-up onto a chip. In doing so, they have met one of the requirements for making it possible to use photonic circuits for optical quantum computers.

Optical quantum computers are what people are pinning their hopes on for tomorrow’s computer technology – whether for tap-proof data encryption, ultrafast...

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

Im Focus: Complex hardmetal tools out of the 3D printer

For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.

Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

European Health Forum Gastein 2016 kicks off today

28.09.2016 | Event News

Laser use for neurosurgery and biofabrication - LaserForum 2016 focuses on medical technology

27.09.2016 | Event News

Experts from industry and academia discuss the future mobile telecommunications standard 5G

23.09.2016 | Event News

 
Latest News

New imaging technique in Alzheimer’s disease - opens up possibilities for new drug development

28.09.2016 | Medical Engineering

Innovate coating extends the life of materials for industrial use

28.09.2016 | Materials Sciences

Blockchain Set to Transform the Financial Services Market

28.09.2016 | Business and Finance

VideoLinks
B2B-VideoLinks
More VideoLinks >>>