Cloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors (original) (raw)
Related papers
The EMBO journal, 1996
The baculovirus inhibitor of apoptosis gene, iap, can impede cell death in insect cells. Here we show that iap can also prevent cell death in mammalian cells. The ability of iap to regulate programmed cell death in widely divergent species raised the possibility that cellular homologs of iap might exist. Consistent with this hypothesis, we have isolated Drosophila and human genes which encode IAP-like proteins (dILP and hILP). Like IAP, both dILP and hILP contain amino-terminal baculovirus IAP repeats (BIRs) and carboxy-terminal RING finger domains. Human ilp encodes a widely expressed cytoplasmic protein that can suppress apoptosis in transfected cells. An analysis of the expressed sequence tag database suggests that hilp is one of several human genes related to iap. Together these data suggest that iap and related cellular genes play an evolutionarily conserved role in the regulation of apoptosis.
Baculoviruses and apoptosis: the good, the bad, and the ugly
Cell Death and Differentiation, 2001
Since 1991, when a baculovirus was first shown to inhibit apoptosis of its host insect cells, considerable contributions to our knowledge of apoptosis have arisen from the study of these viruses and the anti-apoptotic genes they encode. Baculovirus anti-apoptotic genes include p35, which encodes the most broadly acting caspase inhibitor protein known, and iap (inhibitor of apoptosis) genes, which were the first members of an evolutionarily conserved gene family involved in regulation of apoptosis and cytokinesis in organisms ranging from yeast to humans. Baculoviruses also provide an ideal system to study the effects of an apoptotic response on viral pathogenesis in an animal host. In this review, I discuss a number of interesting recent developments in the areas of apoptotic regulation by baculoviruses and the effects of apoptosis on baculovirus replication and pathogenesis. Cell Death and Differentiation (2001) 8, 137 ± 143.
Virology, 2005
The Op-IAP protein from the baculovirus Orgyia pseudotsugata M nucleopolyhedrovirus (OpMNPV) is highly effective at inhibiting apoptosis triggered by a variety of different stimuli in lepidopteran cells as well as in several different mammalian cell types, suggesting that it functions at a highly conserved step in the apoptotic pathway. However, the mechanism by which Op-IAP inhibits apoptosis is unclear. Since some IAP proteins can bind and inhibit caspases, we tested whether Op-IAP could inhibit the activity of caspases from Drosophila melanogaster. We found that recombinant Op-IAP protein was not able to bind or directly inhibit the activity of the Drosophila caspases DRONC, DrICE, or DCP-1 in vitro. In addition, expression of Op-IAP was unable to inhibit apoptosis triggered by either actinomycin D or UV light in D. melanogaster S2 cells. Surprisingly, Op-IAP expression in S2 cells enhanced apoptosis caused by baculovirus infection, but did not cause increased sensitivity to either actinomycin D or UV damage-induced apoptosis. The observation that Op-IAP cannot inhibit these insect caspases suggests that it functions by a mechanism that does not involve direct caspase inhibition.
Impact of Group II Baculovirus IAPs on Virus-Induced Apoptosis in Insect Cells
Genes
Apoptosis plays an important role in virus-host interactions and is a major element of the insect immune response. Exploring the regulatory mechanisms of virus-induced apoptosis through the expression of apoptotic genes holds important research and application value. Functional research on the reported inhibitor of apoptosis proteins (IAPs) mainly focuses on the group I baculovirus, while the functions of the group II baculovirus IAPs remains unclear. To explore its role in the regulation of the apoptosis of insect cells, we constructed the transient expression vector (pIE1 vectors) and the recombinant baculovirus expressing Bsiap genes (from the Buzura suppressaria nucleopolyhedrovirus) of the group II baculovirus. Apoptosis gene expression results and the virus-induced apoptosis rate show that the overexpression of BsIAP1 could promote apoptosis in insect cells. However, the overexpression of BsIAP2 and BsIAP3 decreases the expression of apoptotic genes, revealing an inhibitory ef...
Control of programmed cell death by the baculovirus genes p35 and iap.
Molecular and cellular biology, 1994
The SF-21 insect cell line undergoes rapid and widespread apoptosis when treated with actinomycin D or when infected with a mutant of the baculovirus Autographa californica nuclear polyhedrosis virus lacking a p35 gene or a functionally active iap (inhibitor of apoptosis) gene. Here we provide evidence that the basis for the induction of apoptosis by these two different stimuli is the cessation of RNA synthesis. We also show that expression of eitherp35 or two different functional iap homologs blocks apoptosis independently of other viral genes, indicating that these gene products act directly on the cellular apoptotic pathway. The iap genes encode a C3HC4 (or RING) finger motif found in a number of transcriptional regulatory proteins, as well as two additional Cys/His motifs (baculovirus iap repeats). We show that specific amino acids within both the C3HC4 finger and the N-terminal baculovirus iap repeat are critical for antiapoptosis function. Overexpression of either mammalian bcl-2 or adenovirus EIB-19K, genes which block apoptosis when overexpressed in a number of mammalian cells, does not block actinomycin D-induced apoptosis in SF-21 cells.
Cell, 1995
The 75 kDa tumor necrosis factor receptor (TNFRP) transduces extracellular signals via receptor-associated cytoplasmic proteins. Two of these signal transducers, TRAFl and TRAFP, were isolated and characterized previously. We report here the biochemical purification and subsequent molecular cloning of two novel TNFRZ-associated proteins, designated c-IAPl and c-IAP2, that are closely related mammalian members of the inhibitor of apoptosis protein (IAP) family orginally identified in baculoviruses. The viral and cellular IAPs contain N-terminal baculovirus IAP repeat (BIR) motifs and a C-terminal RING finger. The c-IAPs do not directly contact TNFRS, but rather associate with TRAFl and TRAF2 through their N-terminal BIR motif-comprising domain. The recruitment of c-IAPl or c-IAP2 to the TNFRS signaling complex requires a TRAF2-TRAFl heterocomplex.
Journal of Biological Chemistry, 2011
A novel Arabidopsis thaliana inhibitor of apoptosis was identified by sequence homology to other known inhibitor of apoptosis (IAP) proteins. Arabidopsis IAP-like protein (AtILP) contained a C-terminal RING finger domain but lacked a baculovirus IAP repeat (BIR) domain, which is essential for antiapoptotic activity in other IAP family members. The expression of AtILP in HeLa cells conferred resistance against tumor necrosis factor (TNF)-␣/ActD-induced apoptosis through the inactivation of caspase activity. In contrast to the C-terminal RING domain of AtILP, which did not inhibit the activity of caspase-3, the N-terminal region, despite displaying no homology to known BIR domains, potently inhibited the activity of caspase-3 in vitro and blocked TNF-␣/ActD-induced apoptosis. The antiapoptotic activity of the AtILP N-terminal domain observed in plants was reproduced in an animal system. Transgenic Arabidopsis lines overexpressing AtILP exhibited anti-apoptotic activity when challenged with the fungal toxin fumonisin B1, an agent that induces apoptosis-like cell death in plants. In AtIPL transgenic plants, suppression of cell death was accompanied by inhibition of caspase activation and DNA fragmentation. Overexpression of AtILP also attenuated effector protein-induced cell death and increased the growth of an avirulent bacterial pathogen. The current results demonstrated the existence of a novel plant IAP-like protein that prevents caspase activation in Arabidopsis and showed that a plant anti-apoptosis gene functions similarly in plant and animal systems.
IAPS : More than just inhibitors of apoptosis proteins
Cell Cycle, 2008
Inhibitors of apoptosis proteins (IAPs) are a conserved family of proteins identified in species ranging from virus, yeasts, nematodes, fishes, flies and mammals. The common structural feature is the presence of at least one Baculovirus IAP Repeat (BIR) domain. Hence, IAPs are also known as BIR-containing proteins (BIRCs). Most of them display anti-apoptotic properties when overexpressed. In drosophila, IAPs are sufficient and necessary to promote cell survival through a direct regulation of apoptotic proteases called caspases. In mammals, BIRC4/XIAP, the most studied IAP member can directly inhibit the activity of caspase-3, 7 and 9. However, this activity is not conserved in other IAPs and physiological relevancies of such anti-caspase activities are still discussed. A detailed analysis of IAP-deficient mice or derived cells, deletion experiments performed in drosophila and zebrafish, or research of protein partners have revealed the importance of IAPs in adaptive response to cellular stress, in cell proliferation, differentiation, signaling, motility and in immune response. This review discusses recent data that help understanding of cellular functions of IAPs.