Featured Research

from universities, journals, and other organizations

Protein identified that serves as a switch in a key pathway of programmed cell death

Date:
March 2, 2011
Source:
St. Jude Children's Research Hospital
Summary:
Scientists have identified how cells flip a switch between cell survival and cell death that involves a protein called FLIP.

Work led by St. Jude Children's Research Hospital scientists identified how cells flip a switch between cell survival and cell death that involves a protein called FLIP.

Related Articles


The findings solve a riddle that has puzzled scientists for more than a decade regarding the dual nature of caspase-8, an enzyme intimately linked to the cell's suicide pathway but also essential for cell survival during embryonic development and the immune response. Researchers identified FLIP and the silencing of another enzyme, named RIPK3, as playing pivotal roles. The study was published in the March 2 advance online edition of Nature.

Douglas Green, Ph.D., the paper's senior author and chair of the St. Jude Department of Immunology, said work is already underway to use the findings to generate new cancer treatment targets and fresh insight into the missteps that give rise to certain tumors as well as evidence of how some virus-infected cells escape the pathways designed to dispatch such threats.

"It is a pretty rare thing to 'cure' a lethal mutation in an animal by removing another gene. When that happens, the biology shouts out to us that this is important. We just have to listen," Green said.

FLIP's role was identified after investigators bred mice that lacked genes for both caspase-8 and RIPK3. Previous research identified RIPK3 as responsible for orchestrating cell death via programmed necrosis. Once viewed as an uncontrolled form of cell death, programmed necrosis is now recognized as a distinct form of cell suicide. The body relies on both programmed necrosis and apoptosis, the more common process, to rid itself of damaged, dangerous or unneeded cells.

While loss of caspase-8 was known to be lethal during embryonic development, in this study investigators showed mice that lacked both caspase-8 and RIPK3 were born at normal rates and appeared developmentally normal early in life.

Investigators went on to show that caspase-8 prevents programmed necrosis by combining with FLIP to form an enzyme complex that disrupts RIPK3 functioning and so prevents death via programmed necrosis. The work also demonstrated that FLIP expression prevents caspase-8 from triggering cell death via apoptosis, although the exact mechanism must still be determined. Apoptosis relies on caspase enzymes and other molecules to ensure the cell self destructs.

Green said the findings provide insight into the mechanisms at work in neuroblastoma and other tumors that suffer a loss of caspase-8. "We are beginning collaborative experiments to examine these tumors to see if RIPK3 is deleted or blocked," he said. Neuroblastoma arises in cells of the sympathetic nervous system. It is the most common solid tumor in children, accounting for up to 10 percent of all childhood cancers.

Andrew Oberst, a St. Jude postdoctoral fellow, is the study's first author. The other authors are Christopher Dillon, Ricardo Weinlich, Laura McCormick and Patrick Fitzgerald, all of St. Jude; Cristina Pop and Guy Salvesen, of Sanford-Burnham Medical Research Institute, La Jolla; and Razq Hakem, of the University of Toronto.

The research was supported in part by the National Institutes of Health, the Canadian Institutes of Health Research, the Sass Foundation for Medical Research 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. Andrew Oberst, Christopher P. Dillon, Ricardo Weinlich, Laura L. McCormick, Patrick Fitzgerald, Cristina Pop, Razq Hakem, Guy S. Salvesen, Douglas R. Green. Catalytic activity of the caspase-8–FLIPL complex inhibits RIPK3-dependent necrosis. Nature, March 3, 2011 DOI: 10.1038/nature09852

Cite This Page:

St. Jude Children's Research Hospital. "Protein identified that serves as a switch in a key pathway of programmed cell death." ScienceDaily. ScienceDaily, 2 March 2011. <www.sciencedaily.com/releases/2011/03/110302131855.htm>.
St. Jude Children's Research Hospital. (2011, March 2). Protein identified that serves as a switch in a key pathway of programmed cell death. ScienceDaily. Retrieved March 4, 2015 from www.sciencedaily.com/releases/2011/03/110302131855.htm
St. Jude Children's Research Hospital. "Protein identified that serves as a switch in a key pathway of programmed cell death." ScienceDaily. www.sciencedaily.com/releases/2011/03/110302131855.htm (accessed March 4, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Wednesday, March 4, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Adults Only Get The Flu Twice A Decade, Researchers Say

Adults Only Get The Flu Twice A Decade, Researchers Say

Newsy (Mar. 4, 2015) Researchers found adults only get the flu about once every five years. Scientists analyzed how a person&apos;s immunity builds up over time as well. Video provided by Newsy
Powered by NewsLook.com
Mount Everest Has a Poop Problem

Mount Everest Has a Poop Problem

Buzz60 (Mar. 4, 2015) With no bathrooms to use, climbers of Mount Everest have been leaving human waste on the mountain for years, and it&apos;s becoming a health issue. Mike Janela (@mikejanela) has more. Video provided by Buzz60
Powered by NewsLook.com
Mom Triumphs Over Tragedy, Helps Other Families

Mom Triumphs Over Tragedy, Helps Other Families

AP (Mar. 3, 2015) After her son, Dax, died from a rare form of leukemia, Julie Locke decided to give back to the doctors at St. Jude Children&apos;s Research Hospital who tried to save his life. She raised $1.6M to help other patients and their families. (March 3) Video provided by AP
Powered by NewsLook.com
Looted and Leaking, South Sudan's Oil Wells Pose Health Risk

Looted and Leaking, South Sudan's Oil Wells Pose Health Risk

AFP (Mar. 3, 2015) Thick black puddles and a looted, leaking ruin are all that remain of the Thar Jath oil treatment facility, once a crucial part of South Sudan&apos;s mainstay industry. Duration: 01:13 Video provided by AFP
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