Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Key Protein’s Newly Discovered Form and Function May Provide Novel Cancer Treatment Target

02.05.2012
St. Jude Children’s Research Hospital discovery that a protein vital for cell survival and immune balance has another form with a different function could yield additional cancer treatment strategy

Research led by St. Jude Children’s Research Hospital investigators suggests that safeguarding cell survival and maintaining a balanced immune system is just the start of the myeloid cell leukemia sequence 1 (MCL1) protein’s work.

Nearly 20 years after MCL1 was discovered, scientists have identified a second form of the protein that works in a different location in cells and performs a different function. This newly identified version is shorter and toils inside rather than outside mitochondria where it assists in production of chemical energy that powers cells. The research appears in today’s online edition of the scientific journal Nature Cell Biology.

The finding will likely aid the development of cancer drugs. Many cancers feature high levels of MCL1 or extra copies of the gene, and there is widespread interest in the protein for its potential to treat cancer. Until now, however, those efforts have focused solely on MCL1’s role on the outer mitochondrial membrane, where it blocks cell death via the apoptotic or cell suicide pathway. This study highlights another role.

“We believe this newly identified form of MCL1 that works inside the mitochondria is probably essential for tumor cell survival. If that proves to be correct, then strategies to block the protein from getting into mitochondria offer a new therapeutic approach for cancer treatment,” said Joseph Opferman, Ph.D., an associate member of the St. Jude Department of Biochemistry and a Pew Scholar in the Biomedical Sciences. He is the paper’s senior author.

Opferman has a longstanding interest in MCL1, which belongs to the BCL2 family of proteins that are critical regulators of apoptosis. Unlike other BCL2 proteins, MCL1 is required for embryonic development and for the survival of a variety of normal cell types. The protein is also essential for cancer cell survival.

Until now, however, researchers were unsure how to reconcile MCL1’s varied roles with its status as a member of the BCL2 family of proteins. BCL2 proteins were widely believed to work exclusively on the outer mitochondrial membrane.

“In this study, we show that MCL1 has two forms and two important, but completely different functions,” said Rhonda Perciavalle, Ph.D., a University of Tennessee Health Science Center graduate student in Opferman’s laboratory and the study’s first author. Along with working on the outer mitochondrial membrane to help protect cells from apoptosis, investigators demonstrated that MCL1 works internally to facilitate mitochondrial energy production in the mitochondrion’s matrix.

Using a variety of laboratory techniques, researchers showed that inside the mitochondrion, MCL1 promotes the normal structure of the inner membrane, where much of the work of energy production is done. The loss of the inner mitochondrial form of MCL1 hampers the ability of cells to produce energy, thus impeding their ability to proliferate.

“The results help explain why the loss of this single pro-survival molecule, MCL1, has such a dramatic impact. We are now working with tumor models to determine if this newly identified form of MCL1 is essential for cancer cells,” Opferman said. Perciavalle said the two forms might work together to protect cancer cells from apoptotic death and to provide them with the fuel and nutrients to sustain their unchecked growth and spread.

Work is also underway to learn precisely how MCL1 functions inside the mitochondria in both normal and cancer cells. Investigators are also interested in the relative importance of the two versions of MCL1 in different tissues under a variety of different conditions.

The other authors are Daniel Stewart, Brian Koss, John Lynch, Sandra Milasta, Madhavi Bathina, Jamshid Temirov, Stephane Pelletier, John Schuetz and Douglas Green, all of St. Jude; and Megan Cleland and Richard Youle, of the National Institute of Neurological Disorders and Stroke.

The research was funded in part by the National Institutes of Health, the American Cancer Society, a National Cancer Institute Cancer Center Support Grant and ALSAC.

St. Jude Children’s Research Hospital
Since opening 50 years ago, St. Jude Children’s Research Hospital has changed the way the world treats childhood cancer and other life-threatening diseases. No family ever pays St. Jude for the care their child receives and, for every child treated here, thousands more have been saved worldwide through St. Jude discoveries. The hospital has played a pivotal role in pushing U.S. pediatric cancer survival rates from 20 to 80 percent overall, and is the first and only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. It is also a leader in the research and treatment of blood disorders and infectious diseases in children. St. Jude was founded by the late entertainer Danny Thomas, who believed that no child should die in the dawn of life. To learn more, visit www.stjude.org. Follow us on Twitter @StJudeResearch.
St. Jude Public Relations Contacts
Summer Freeman
(desk) 901-595-3061
(cell) 901-297-9861
summer.freeman@stjude.org
Carrie Strehlau
(desk) 901-595-2295
(cell) 901-297-9875
carrie.strehlau@stjude.org

Summer Freeman | Newswise Science News
Further information:
http://www.stjude.org

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>