LIFE AND DEATH DECISIONS - THE ROLE OF THE IAPS IN MODULATING PROGRAMMED CELL-DEATH

Multicellular organisms have evolved elaborate signal transduction pat hways for maintaining homeostasis through the control of cell prolifer ation and death. The recent surge of interest in the regulation of pro grammed cell death has led to the rapid identification of many protein s involved in controlling and executing apoptosis. The inhibitors of a poptosis proteins (IAPs) constitute a family of highly conserved death suppressing proteins that were first identified in baculoviruses, and that has recently expanded to include at least two homologues in Dros ophila melanogaster and four in rodents and humans, In this article we review the current state of IAP research. Two of the IAPs, HIAP-1 and HIAP-2, have been placed within the TNF alpha induced cell death path way which involves two receptors for TNF alpha and multiple, overlappi ng signal transduction proteins. A third, X-linked gene termed XIAP, i s ubiquitously expressed and appears to have a broad range of suppress or activity to a variety of apoptotic triggers. The fourth member, NAI P, has been identified as the protein product of a candidate gene for the inherited neuromuscular disorder, spinal muscular atrophy (SMA). T he neuroprotective activity of NAIP in an in vivo model of cerebral is chemia has also been demonstrated.