Genomic Organization of the X-linked Inhibitor of Apoptosis and Identification of a Novel Testis-Specific Transcript

The inhibitors of apoptosis: there is more to life than Bcl2

“…HIAP1), and X-chromosome-linked IAP (XIAP), all of which contain three BIR domains and a carboxy-terminal RING finger (Rothe et al, 1995;Duckett et al, 1996;Liston et al, 1996;Uren et al, 1996). The family continued to expand with the identification of Survivin (single BIR, Lin et al, 2000;Vucic et al, 2000;Kasof and Gomes, 2001), and testis-specific IAP (Ts-IAP; single BIR and carboxy-terminal RING finger; Lagace et al, 2001;Richter et al, 2001). Table 1 summarizes the names, domain structure and interactions of the IAP family members, with the protein domains illustrated schematically in Figure 1.…”

“…Ts-IAP is an autosomal, retrotransposed, intronless copy of XIAP, and is expressed solely in the testis (Lagace et al, 2001;Richter et al, 2001). There are examples of other X-chromosome-linked genes having retrotransposed autosomal copies.…”

IRES in distress: translational regulation of the inhibitor of apoptosis proteins XIAP and HIAP2 during cell stress

“…The mammalian family of IAPs includes XIAP, HIAP1, HIAP2, NAIP, Survivin, Livin, BRUCE, and Ts-IAP. [10][11][12][13][14][15][16] The IAPs have a characteristic baculovirus IAP repeat (BIR) domain that consists of a zinc-finger motif, and several IAP proteins contain multiple BIR domains (Figure 1). Most importantly, the interaction between IAP and caspase that blocks caspase activity occurs via the region of the IAP that contains the BIR domains.…”

IAP proteins: sticking it to Smac

“…The study by Vucic et al [11] is an elegant structural characterization of ML-IAP (melanoma IAP [14]), and the study by Shin et al [12] examines the structural and functional properties of human ILP-2 (IAP-like protein 2; also known as BIRC8 [15,16]) and our group has examined the protective properties of a baculoviral IAP (Op-IAP [17]). The first study shows that, despite its strongly protective properties, ML-IAP is significantly inferior to XIAP in terms of caspase inhibition, but has a very high affinity for Smac.…”

“…We have reported that the ILP-2 gene is found only in great apes [15], and that where it is found the open reading frame is conserved, but definitive proof of the existence of ILP-2 has been hampered by its extremely close similarity to XIAP, and to the existence of a widely expressed proteolytic fragment of XIAP which is virtually indistinguishable from ILP-2 [18]. The stabilization of ILP-2 by the addition of nine unrelated residues at the N-terminus is reminiscent of the use, in the two papers describing the functional properties of this factor, of synthetic Nterminal epitope tags [15,16]. Diplomatically, the authors of the present studies [12] suggest that ILP-2 may require a (currently unidentified) testis-specific stabilizing protein or chaperone to be fully functional, although the alternative possibility must be considered, namely that ILP-2 might simply be the product of an expressed pseudogene.…”