A guardian angel of cell integrity

摘要

The saying, "while you do not know life, how can you know death?" from the great Chinese philosopher Confucius, encapsulates the human desire to understand matters of life and death. Beyond philosophical curiosity, at the cellular level the balance between life and death is essential for health. Mutations in genes that regulate cell death have been found to cause human diseases ranging from inflammation and autoimmunity to cancer. Normally, cell-death genes have dedicated roles in either cell survival or cell death. But in this issue, two groups show that receptor interacting protein kinase 1 (RIPK1), a factor known to promote cell death, has a paradoxical function in supporting the survival of the epithelial cells that line our body's cavities and skin surfaces. Since the discovery of RIPK1 almost 20 years ago, the proposed function of the protein has alternated between that of a cell-death promoter and a cell-death inhibitor. Much of what we know about RIPK1 biology comes from studies of its activation by the tumour-necrosis factor (TNF) receptor, a cell-surface protein that, when bound by TNF molecules, contributes to inflammation, cell differentiation and cell death. Genetically modified mice that lack RIPK1 die shortly after birth, and this was thought to be due to failure to stimulate NF-_κB, a cellular factor that turns on the expression of survival genes. Consistent with this idea, extensive cell death and inflammation in multiple tissues occur in these RIPK1 -deficient mice.