Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes

TLDR: A NAIP-mediated inhibition of apoptosis induced by a variety of signals is demonstrated, and three additional human complementary DNAs and a Drosophila melanogaster sequence that are also homologous to the baculovirus lAPs are identified.

Abstract: DYSREGULATION of apoptosis can result in inappropriate suppression of cell death, as occurs in the development of some cancers1, or in failure to control the extent of cell death, as is believed to occur in acquired immunodeficiency and certain neurodegenera-tive disorders, such as spinal muscular atrophy (SMA). Recently, we isolated a candidate gene, encoding neuronal apoptosis inhibitor protein (NAIP)2, for SMA. This gene is homologous to two baculovirus inhibitor of apoptosis proteins3,4(Cp-IAP and Op-IAP) and is partly deleted in individuals with type I SMA. A second SMA candidate gene encoding survival motor neuron (SMN), which is contiguous with the NAIP locus on 5ql3.1, was also reported5. Here we demonstrate a NAIP-mediated inhibition of apoptosis induced by a variety of signals, and have identified three additional human complementary DNAs and a Drosophila melanogaster sequence that are also homologous to the baculovirus lAPs. The four open reading frames (ORFs) possess three baculoviral inhibition of apoptosis protein repeat (BIR) domains and a carboxy-terminal RING zinc-finger. The human iap genes have a distinct but overlapping pattern of expression in fetal and adult tissues. These proteins significantly increase the number of known apoptotic suppressors.