Featured Research

from universities, journals, and other organizations

Key protein's newly discovered form and function may provide novel cancer treatment target

Date:
April 30, 2012
Source:
St. Jude Children's Research Hospital
Summary:
Scientists' discovery that a protein vital for cell survival and immune balance has another form with a different function could yield additional cancer treatment strategy. 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.

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 recently appeared in  the 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.


Story Source:

The above story is based on materials provided by St. Jude Children's Research Hospital. Note: Materials may be edited for content and length.


Journal Reference:

  1. Rhonda M. Perciavalle, Daniel P. Stewart, Brian Koss, John Lynch, Sandra Milasta, Madhavi Bathina, Jamshid Temirov, Megan M. Cleland, Stιphane Pelletier, John D. Schuetz, Richard J. Youle, Douglas R. Green, Joseph T. Opferman. Anti-apoptotic MCL-1 localizes to the mitochondrial matrix and couples mitochondrial fusion to respiration. Nature Cell Biology, 2012; DOI: 10.1038/ncb2488

Cite This Page:

St. Jude Children's Research Hospital. "Key protein's newly discovered form and function may provide novel cancer treatment target." ScienceDaily. ScienceDaily, 30 April 2012. <www.sciencedaily.com/releases/2012/04/120430105033.htm>.
St. Jude Children's Research Hospital. (2012, April 30). Key protein's newly discovered form and function may provide novel cancer treatment target. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2012/04/120430105033.htm
St. Jude Children's Research Hospital. "Key protein's newly discovered form and function may provide novel cancer treatment target." ScienceDaily. www.sciencedaily.com/releases/2012/04/120430105033.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How Nigeria Beat Its Ebola Outbreak

How Nigeria Beat Its Ebola Outbreak

Newsy (Oct. 20, 2014) — The World Health Organization has declared Nigeria free of Ebola. Health experts credit a bit of luck and the government's initial response. Video provided by Newsy
Powered by NewsLook.com
Another Study Suggests Viagra Is Good For The Heart

Another Study Suggests Viagra Is Good For The Heart

Newsy (Oct. 20, 2014) — An ingredient in erectile-dysfunction medications such as Viagra could improve heart function. Perhaps not surprising, given Viagra's history. Video provided by Newsy
Powered by NewsLook.com
Ebola Worries End for Dozens on U.S. Watch Lists

Ebola Worries End for Dozens on U.S. Watch Lists

Reuters - US Online Video (Oct. 20, 2014) — Forty-three people who had contact with Thomas Eric Duncan, the first person diagnosed with Ebola in the U.S., were cleared overnight of twice-daily monitoring after 21 days of showing no symptoms. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Fauci: Ebola Protocols to Focus on Training

Fauci: Ebola Protocols to Focus on Training

AP (Oct. 20, 2014) — Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, says he expects revised CDC protocols on Ebola to focus on training, observation and ensuring health care workers are more protected. (Oct. 20) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins