Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes.
Dysregulation of apoptosis can result in inappropriate suppression of cell death, as occurs in the development of some cancers, or in failure to control the extent of cell death, as is believed to occur in acquired immunodeficiency and certain neurodegenerative disorders, such as spinal muscular atrophy (SMA). Recently, we isolated a candidate gene, encoding neuronal apoptosis inhibitor protein (NAIP), for SMA. This gene is homologous to two baculovirus inhibitor of apoptosis proteins (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 5q13.1, was also reported. 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 IAPs. 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.
Liston
P
P
Molecular Genetics Research Laboratory, Children's Hospital of Eastern Ontario, Ottawa, Canada.
Roy
N
N
Tamai
K
K
Lefebvre
C
C
Baird
S
S
Cherton-Horvat
G
G
Farahani
R
R
McLean
M
M
Ikeda
J E
JE
MacKenzie
A
A
Korneluk
R G
RG
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D016367:Baculoviridae / Q000235:genetics; D001483:Base Sequence; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D017931:DNA Primers; D018076:DNA, Complementary; D004331:Drosophila melanogaster / Q000235:genetics; D005333:Fetus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D009134:Muscular Atrophy, Spinal / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D051616:Neuronal Apoptosis-Inhibitory Protein; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014764:Viral Proteins / Q000235:genetics; D014812:Vitamin K / Q000494:pharmacology; D016335:Zinc Fingers / Q000235:genetics
D017931:DNA Primers; D018076:DNA, Complementary; D051034:Inhibitor of Apoptosis Proteins; C496800:NAIP protein, human; C496801:Naip1 protein, mouse; D009419:Nerve Tissue Proteins; D051616:Neuronal Apoptosis-Inhibitory Protein; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus; D014812:Vitamin K