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:6/7/2016)... TORONTO , June 7, 2016  Syngrafii ... begun a business relationship that includes integrating Syngrafii,s ... pilot branch project. This collaboration will result in ... for the credit union, while maintaining existing document ... http://photos.prnewswire.com/prnh/20160606/375871LOGO ...
(Date:6/1/2016)... Favorable Government Initiatives Coupled With ... Identification to Boost Global Biometrics System Market Through 2021  ... report, " Global Biometrics Market By Type, By ... 2011 - 2021", the global biometrics market is projected ... of growing security concerns across various end use sectors ...
(Date:5/9/2016)... May 9, 2016 Elevay is ... to expanding freedom for high net worth professionals seeking ... today,s globally connected world, there is still no substitute ... ever duplicate sealing your deal with a firm handshake. ... by taking advantage of citizenship via investment programs like ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... ... June 27, 2016 , ... Rolf K. Hoffmann, former senior ... the University of North Carolina Kenan-Flagler Business School effective June 27. ... Kenan-Flagler, with a focus on the school’s international efforts, leading classes and participating ...
(Date:6/24/2016)... , June 24, 2016 Epic Sciences ... detects cancers susceptible to PARP inhibitors by targeting ... cells (CTCs). The new test has already been ... in multiple cancer types. Over 230 ... damage response pathways, including PARP, ATM, ATR, DNA-PK ...
(Date:6/23/2016)... WI (PRWEB) , ... June 23, 2016 , ... ... supplements, is pleased to announce the launch of their brand, UP4™ Probiotics, into ... for over 35 years, is proud to add Target to its list of ...
(Date:6/23/2016)... Houston Methodist Willowbrook Hospital has signed ... to serve as their official health care provider. ... will provide sponsorship support, athletic training services, and ... volunteers, athletes and families. "We are ... and to bring Houston Methodist quality services and ...
Breaking Biology Technology: