IAPS : More than just inhibitors of apoptosis proteins

Abstract

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.

Making a definitive diagnosis: Successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease

“…12 The XIAP protein has a central role in the proinflammatory response, leading to activation of NFkB and subsequent activation of proinflammatory cytokines via the NOD signaling pathway, as well as a crucial role in mediating programmed cell death. [13][14][15] Functionally testing these pathways in the patient's cells provided results consistent with aberrant XIAP function: muramyl dipeptide stimulation of patient's PBMCs was unable to induce the expression of IL-8 compared with controls (Fig. 4A), and CD3 stimulation of PBMC blasts resulted in enhanced apoptosis in the patient compared with controls (Fig.…”

Variations in the protein level of Omi/HtrA2 in the heart of aged rats may contribute to the increased susceptibility of cardiomyocytes to ischemia/reperfusion injury and cell death

“…The BIR2 domain of XIAP inhibits caspase-3 and caspase-7, while BIR3 binds to and inhibits caspase-9. The RING domain utilizes E3 ubiquitin ligase activity and enables IAPs to catalyze ubiquitination of self, caspase-3, or caspase-7 (Dubrez-Daloz et al 2008). It has been demonstrated that in the failing human heart, XIAP is downregulated, indicating that the cardiomyocytes were more sensitive to apoptosis (Haider et al 2009).…”

X-linked Inhibitor of Apoptosis Protein (XIAP) Regulation of Cyclin D1 Protein Expression and Cancer Cell Anchorage-independent Growth via Its E3 Ligase-mediated Protein Phosphatase 2A/c-Jun Axis

“…Played an Important Role in Anchorage-independent Growth and Cell Cycle G 1 /S Progression of Colon Cancer Cells-It has been verified that XIAP has additional biological functions that do not rely on its inhibition of apoptosis (12,33). To delineate the biological significance of XIAP in cancer cell proliferation, HCT116 XIAP-deficient (XIAPϪ/Ϫ) transfectants with XIAP (HA-XIAP) and XIAP H467A, a point mutation resulting in loss of its E3 ubiquitin ligase activity (34), were seeded in soft agar for determination of its anchorage-independent growth capability compared with WT(vector) and XIAPϪ/Ϫ(vector).…”