Navigation Links
Key protein's newly discovered form and function may provide novel cancer treatment target
Date:4/30/2012

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.


'/>"/>

Contact: Summer Freeman
summer.freeman@stjude.org
901-595-3061
St. Jude Children's Research Hospital
Source:Eurekalert

Related biology news :

1. Gold nanoantennas detect proteins
2. More effective method of imaging proteins
3. Proteins behaving badly
4. ORNL explores proteins in Yellowstone bacteria for biofuel inspiration
5. Faulty proteins may prove significant in identifying new treatments for ovarian cancer
6. Penn scientists pioneer new method for watching proteins fold
7. Lets do the twist: Spiral proteins are efficient gene delivery agents
8. Control by the matrix: RUB researchers decipher the role of proteins in the cell environment
9. Cellular processing of proteins found in Congolese child birthing tea now revealed
10. Targeted antibacterial proteins may offer antibiotic alternative
11. New technique enables study of challenging proteins
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/21/2017)... and PORTLAND, Ore. , ... and the Avamere Family of Companies (Avamere Health Services, ... announced a six-month research study that will apply the ... eldercare at senior living and health centers. By analyzing ... hopes to gain insights into physical and environmental conditions, ...
(Date:2/14/2017)... N.C. , Feb. 14, 2017  Wake Forest ... M.D., as its new chief executive officer (CEO). Freischlag ... CEO John D. McConnell , M.D., who last ... position at the Medical Center, after leading it since ... the full scope of Wake Forest Baptist,s academic health ...
(Date:2/10/2017)... -- Research and Markets has announced the ... Scientific and Commercial Aspects" to their offering. ... Biomarkers play ... therapy for selection of treatment as well for monitoring the ... disease in modern medicine. Biochip/microarray technologies and next generation sequencing ...
Breaking Biology News(10 mins):
(Date:3/24/2017)... Mar. 24, 2017 Research and Markets has ... Research - Global Strategic Business Report" report to their offering. ... This report ... in US$ Million. Annual estimates and forecasts are provided for the ... primary and secondary research. The report profiles 25 ...
(Date:3/24/2017)... , March 24, 2017 ... the trading session at 5,817.69, down 0.07%; the Dow ... 20,656.58; and the S&P 500 closed at 2,345.96, marginally ... 4 sectors closed in green, 4 sectors finished in ... This Friday, Stock-Callers.com has initiated reports coverage on the ...
(Date:3/24/2017)... , March 24, 2017 Agenus Inc. (NASDAQ: ... checkpoint antibodies and cancer vaccines, today announced participation at ... th  Annual William Blair and Maidstone Life Sciences conference ... Center in New York, NY . ... March 29 at 9:40 am: Robert B. Stein ...
(Date:3/23/2017)... ... 2017 , ... Lajollacooks4u is proud to announce it has become the premiere team-building cooking event ... companies around the world, such as Illumina, HP and Qualcomm, and is ranked #1 in ... popularity is due to its new team building format, a way for teams to not ...
Breaking Biology Technology: