ESCRT-III Acts Downstream of MLKL to Regulate Necroptotic Cell Death

A research team led by St. Jude Children's Research Hospital immunologists has discovered how a set of proteins delays the "executioner" machinery that kills damaged or infected cells in a process called necroptosis. The scientists believe the finding may have wide clinical implications if researchers can develop drugs to control the cellular rescue machinery. Rescue treatments that prevent necroptosis in transplanted organs could reduce injury to the transplant caused by lack of oxygen, researchers said. Drugs to rescue cells from necroptosis could also help prevent injuries to tissue deprived of blood by heart attack and stroke. In such cases, restoring blood flow and oxygenation triggers inflammation that kills tissue. The researchers said cell-rescuing drugs could also thwart cancer spread by protecting blood vessel cells from being killed by tumor cells. Tumor cells escape the bloodstream to spread in the body by killing blood vessels. Blocking the rescue machinery might also prove useful in treating cancers, by enhancing death of cancer cells by necroptosis. In treating neurodegenerative disorders such as ALS--also known as Lou Gehrig's Disease--activating the rescue machinery could help prevent death of brain cells. And in treating viral infections such as influenza, rescue treatment could extend the life of cells infected by the virus, so that the body's immune system would be more strongly alerted to fight the infection. The researchers were led by Douglas Green, Ph.D., Chair of the St. Jude Department of Immunology. The first author was Yi-Nan Gong, Ph.D., a scientist in Dr. Green's laboratory. The research appears in the the April 6, 2017 issue of the prestigious journal Cell.
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