Immunology

St. Jude Children's Research Hospital solves mystery of enzyme's role in cell survival, offering clues of how immune system fights infection and possible strategies to treat problems ranging from heart attack to cancer.

Researchers have demonstrated that an enzyme required for animal survival after birth functions like an umpire, making the tough calls required for a balanced response to signals that determine if cells live or die. St. Jude Children's Research Hospital scientists led the study, which was published online and appears in the May 22 edition of the scientific journal Cell.

The work involved the enzyme receptor-interacting protein kinase 1 (RIPK1). While RIPK1 is known to be involved in many vital cell processes, this study shows that its pivotal role in survival after birth is as an inhibitor of two different pathways that lead to the death of cells. Functioning properly, the pathways provide a way to get rid of dangerous, damaged or unneeded cells.

By removing different components of each pathway in different combinations, researchers demonstrated that after birth RIPK1 helps cells maintain a balanced response to signals that promote either pathway. "We are learning that in disease this balancing act can be perturbed to produce damage and cell death," said the study's corresponding author Douglas Green, Ph.D., chair of the St. Jude Department of Immunology.

The results resolve long-standing questions about RIPK1's role in cell survival and provide clues about how the disease-fighting immune system might use these pathways to contain infections. The findings have also prompted researchers to launch an investigation into whether RIPK1 could be harnessed to kill cancer cells or provide insight into tumor development. RIPK1 is already the focus of drug development efforts designed to limit cell damage following heart attack, stroke or kidney injury.

"This study fundamentally changes the way we think about RIPK1, a molecule that we care about because it is required for life," Green said. "The results helped us identify new pathways involved in regulating programmed cell death and suggest that we might be able to develop cancer therapies that target these the pathways or engage them in other ways to advance treatment of a range of diseases."

The study is one of two involving RIPK1 being published in the same edition of Cell.