A new family of apoptotic cell death inhibitors

Apoptosis, or programmed cell death, is a process by which cells can be eliminated without eliciting an inflammatory immune response. This is the mechanism used to delete immature T cells in the thymus and to eliminate activated immune cells once they are no longer needed for an immune re sponse. We have recently identified a novel gene family involved in regulation of apoptosis. The family members are homologous to the baculovirus iap gene, and are characterized by 3 amino terminal baculoviral iap repeats (BIRs), containing cysteine-histidine motifs, and a carboxy terminal RING finger domain, believed to be involved in protein-protein interactions. We cloned one gene from Drosophila and one from human. The genes are highly conserved both to each other and to the viral gene. In addition, there is evidence that the gene products of this family associate with the tumor necrosis factor (TNF) receptor complex. The role of the IAP-like protein (ILP) family members has not been completely elucidated. The genes we have cloned are widely expressed and we have shown that hILP is able to prevent ICE-rnediated programmed cell death. In order to gain further understanding of the role of this protein, we are presently in the process of disrupting the murine version of the hILP gene through gene targeting.

Duke Scholars

Author Colin S Duckett Pathology