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

Abstract

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.

The inflammasomes in health and disease: from genetics to molecular mechanisms of autoinflammation and beyond

“…IPAF contains a CARD, whereas NAIP includes three baculovirus inhibitor domains that are probably involved in inhibition of apoptosis. 20 Both IPAF and NAIP are involved in the formation of inflammasomes. Whole bacteria, such as Salmonella typhimurium, Pseudomonas aeruginosa or Legionella pneumophila, as well as bacterial components including flagellin, also promote IPAF oligomerization resulting in recruitment and activation of caspase-1.…”

Mdm2: keeping p53 under control

“…Identical residues are shadowed in dark grey whereas similar residues are in light grey. CNEU is the neuralized homolog of Caenorhabditis elegans (Wilson and al., 1994); DNEU is neuralized from Drosophila melanogaster (Boulianne et al, 1991); IAP homologs are from the following species: IAPC, Cydia pomonella granulosis virus (Crook et al, 1993); IAPO, Orgyia pseudotsugata nuclear polyhedrosis virus (Birnbaum et al, 1994); IAPA, Autographa californica nuclear polyhedrosis virus (Ayres et al, 1994); DIAP, Drosophila melanogaster (Liston et al, 1996); XIAP, HIAP1 and HIAP2, Homo sapiens (Liston et al, 1996) and MIAP2, Mus musculus (Rothe et al, 1995) Fingers: what for?…”

“…The ring®ngers showing the greatest homology with those of Mdm2 in regard to both the primary sequence and the exact location with respect to the C-terminus are the ring-®ngers of two classes of proteins represented by neuralized and IAP (Boulianne et al, 1991;Crook et al, 1993;Figure 4). Neuralized was shown to be involved in neurogenesis in Drosophila, while IAP proteins are a large family of proteins with antiapoptotic activity which are represented in both vertebrates and invertebrates (Liston et al, 1996). The exact function of the ring-®nger in these proteins is not known.…”

Oncolytic adenovirus-mediated shRNA against Apollon inhibits tumor cell growth and enhances antitumor effect of 5-fluorouracil

“…[1][2][3][4][5] A hallmark of IAPs is the presence of one to three baculovirus IAP repeat (BIR) domains, through which the IAPs bind and thereby inhibit caspases. [6][7][8] Certain IAPs (such as mammalian proteins XIAP, CIAP1, CIAP2 and ML-IAP) also possess a C-terminal RING finger, which can act as E3 ubiquitinligases and might enable IAPs to ubiquitylate proteins that interact with them directly and target them for degradation by the proteasome.…”