Navigation Links
Protein Targeted For Cancer Drug Development Is Essential For Normal Heart Function
Date:7/10/2013

MEMPHIS, Tenn., July 10, 2013 /PRNewswire-USNewswire/ -- St. Jude Children's Research Hospital scientists have discovered that a protein used by cancer cells to evade death also plays a vital role in heart health. This dual role complicates efforts to develop cancer drugs that target the protein, but may lead to new therapies for heart muscle damage. The research appeared in the June 15 edition of the scientific journal Genes & Development.

The protein, MCL1, is currently the focus of widespread cancer drug development efforts. MCL1 is best known as an inhibitor of death via the cell's suicide pathway in a process called apoptosis. The protein is elevated in a variety of cancers, and a number of MCL1 inhibitors are in the cancer drug development pipeline worldwide. The protein has also been linked to drug resistance in cancer patients. Until now, however, MCL1's role in heart muscle cells was unclear.

"Our study shows that MCL1 is required for normal cardiac function and that the protein may be critical in protecting the heart from apoptosis," said Joseph Opferman, Ph.D., an associate member of the St. Jude Department of Biochemistry and the paper's corresponding author. Unlike skin or blood cells, heart muscle cells cannot be replaced, so even a small loss through apoptosis can be devastating. In this study, knocking out MCL1 in mice led to death from cardiomyopathy within weeks.

"These findings suggest that cancer-related drug development efforts should focus on reducing MCL1 expression in target cells rather than eliminating the protein's function completely," Opferman said.

The results also have implications for treating heart muscle damage following heart attacks or other insults. While limiting MCL1 in cancer cells might aid in destroying them, providing higher levels of the protein in heart muscle cells might benefit a patient recovering from a heart attack or other heart damage. "These findings have broad implications for human health," Opferman said.

MCL1 belongs to a protein family involved in regulating apoptosis. The body uses apoptosis to rid itself of damaged, dangerous or unneeded cells. MCL1 prevents apoptosis by blocking the activity of other members of the same protein family that promote the process.

This research builds on previous work from Opferman's laboratory that identified a second form of MCL1. That form works inside rather than outside the mitochondria and helps to produce the chemical energy that fuels cells. Mitochondria are specialized structures inside cells that serve as their power plants.

The latest results suggest both forms of MCL1 are necessary for normal heart function, said the paper's first author Xi Wang, a University of Tennessee Health Science Center graduate student working in Opferman's laboratory.

When investigators knocked out the mouse version of the human MCL1 gene in the heart and skeletal muscle of both embryonic and adult mice, the animals rapidly developed lethal cardiomyopathy. Without MCL1, researchers found that muscle fiber in heart muscle cells was replaced by fibrous tissue, and the pumping ability of the animals' hearts diminished. Loss of MCL1 was also associated with a rise in apoptosis sufficient to cause fatal heart muscle weakness.

To better understand MCL1's role in normal heart function, researchers blocked apoptosis by deleting genes for the proteins Bak and Bax as well as MCL1. Bak and Bax promote apoptosis. Knocking out all three genes restored normal heart function in the mice. The animals lived longer, but mitochondria in the heart muscle did not look or function normally. These results suggest that normal heart function requires both forms of MCL1. "The question is whether, with time, you would see deleterious effects from the loss of MCL1 separate from apoptosis," Opferman said.

The other authors are Madhavi Bathina, John Lynch, Brian Koss, Christopher Calabrese, Sharon Frase, John Schuetz and Jerold Rehg, all of St. Jude.

The research was funded in part by a grant (HL102175) from the National Institutes of Health (NIH), a grant (CA021765) from the National Cancer Institute (NCI) at the NIH, the National Cancer Society and ALSAC.


'/>"/>
SOURCE St. Jude Children's Research Hospital
Copyright©2012 PR Newswire.
All rights reserved

Related medicine technology :

1. ImmunGene and Collaborators Report Positive Results in Pre-clinical Studies of Novel Anti-CD20 Antibody-Interferon Alpha Fusion Protein
2. Protein Sciences Prepared to Combat the Latest Potential Pandemic Flu Virus
3. Omega Protein Announces First Quarter 2013 Earnings Conference Call
4. Oramed Pharmaceuticals Granted Japanese Patent for its Core Technology in Oral Delivery of Proteins
5. Therapeutic Proteins to 2016: Drugs, Devices, Diseases, Markets and Forecasts
6. Sigma-Aldrich Corporations Sigma Life Science Business to Distribute Worldwide Olink Biosciences Protein Interaction Analysis Technology
7. Epizyme Publishes Current Review on Targeting Protein Methyltransferases for Personalized Cancer Therapeutics
8. Novel Apolipoprotein A-I Therapy, CSL112, May Represent New Option for Reducing Recurrent Heart Attack Risk, Early CSL Studies Show
9. Advantages of Pressure BioSciences PCT Platform Highlighted at a Recent International Scientific Conference Focused on the Role of Proteins in the Cause, Prevention, and Treatment of Disease
10. ProteinSimple Charges Ahead with the Simple Western
11. Ventana Medical Systems, Inc. develops first-ever fully automated dual-stain technique for miRNA and protein detection in cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/21/2017)... Jan. 20, 2017  Faruqi & Faruqi, LLP, a leading ... or the "Company") (NASDAQ: KMPH ) of the ... certain officers and directors and underwriters of the Company,s April ... role of lead plaintiff. The lawsuit has been ... for Johnson County on behalf of ...
(Date:1/20/2017)... , January 20, 2017 Stock-Callers.com ... (NASDAQ: SGYP ), Novo Nordisk A/S (NYSE: ... ), and Pernix Therapeutics Holdings Inc. (NASDAQ: PTX ... on Thursday, January 19 th , 2017, finishing near its ... Care Index dropped over 0.7%, while shares of health care ...
(Date:1/20/2017)... 20, 2017 Entscheidung ... Nothilfe   Die internationale humanitäre Stadt soll um ... schaffen   Seine Hoheit Scheich Muhammad ... sowie Herrscher von Dubai , hat ... Hilfe (International Humanitarian City IHC) zu verdreifachen, um den ...
Breaking Medicine Technology:
(Date:1/20/2017)... ... 20, 2017 , ... Source Vitál Apothecary, a skin and body care company ... the company had a successful visit to the 2017 ECRM Diet, Vitamin & Sports ... work in the nutritional, sports and health industries a chance to meet in private ...
(Date:1/20/2017)... ... 20, 2017 , ... ATP Science, an Australian-based company focused ... the January ECRM Trade Show in Hilton Head, SC, benefiting from outstanding meetings ... of supplements that keep the body functioning at its peak performance by providing ...
(Date:1/20/2017)... York, NY (PRWEB) , ... January 20, 2017 ... ... – VW+ 001 and its sugar-free alternative VW+ 002. The drinks have been ... body with optimal conditions to perform during your workout. , After a successful ...
(Date:1/20/2017)... ... January 20, 2017 , ... “I Forgive You”: a fine examination of how God handles ... the creation of published author, Stephen Miller, who, for over ten long years has been ... him. Born in Trinidad and Tobago, he has been serving the Lord for over twenty ...
(Date:1/20/2017)... ... January 20, 2017 , ... “Knowledge is God’s Lighthouse”: a ... “Knowledge is God’s Lighthouse” is the creation of published author, Gene Gaapf, a retired ... collections. , “I have been writing since high school and have many different ...
Breaking Medicine News(10 mins):