Anti-XIAP

XIAP [human X-linked IAP, hILP (human IAP-like protein), MIHA, BIRC4) is a member of the family of inhibitor of apoptosis proteins (IAP). IAPs suppress mitochondria-dependent and independent apoptosis by binding to and inhibiting caspases through their BIR domains (reviewed in Liston et al, 2003, Wright and Duckett, 2005). Resistance towards apoptosis is a hallmark of cancer cells, and overexpression of IAPs can contribute to the development of cancer though inhibiting apoptosis. In addition to at least one BIR domain, some IAP members also have a RING-type finger motif at their carboxyl-terminal. The RING finger domain of several IAPs, including XIAP, have E3 ubiquitin ligase activity and target the degradation of Smac/DIABLO through ubqiuitination (Morizane et al, 2005). Smac/DIABLO is a death inducer and functions by inhibiting IAP-caspase interactions, thereby promoting apoptosis. Degradation of cell death inducers like Smac/DIABLO is thought to be a conserved mechanism by which IAPs enhance their anti-apoptotic activity, thereby promoting cell survival. XIAP is highly characterized with respect to its structure and biochemical mechanisms, and has received interest as a therapeutic target (reviewed in Schimmer, 2006). Since XIAP blocks a substantial portion of the apoptosis pathway and is associated with chemoresistance in cancer cells, inhibiting XIAP has been a focus for potential therapeutics. Approaches have included antisense oligonucleotides and small molecule inhibitors. Small molecules that that target the BIR2 and BIR3 domains of XIAP are considered particularly attractive. This is because the BIR domains inhibit caspase activity, and it is thought that removing the inhibition should increase the cell's ability to undergo apoptosis as well as decrease its potential for chemoresistance. This antibody recognizes XIAP. Full-length human XIAP is a 497 amino acid protein and migrates at approx. 53 kDa on SDS-PAGE. Protein function: Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis. Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it in a monomeric, inactive state. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, CASP3, CASP7, CASP8, CASP9, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS and BIRC5/survivin. Ubiquitinion of CCS leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation. Ubiquitinion of MAP3K2/MEKK2 and AIFM1 does not lead to proteasomal degradation. Plays a role in copper homeostasis by ubiquitinationg COMMD1 and promoting its proteasomal degradation. Can also function as E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Regulates the BMP signaling pathway and the SMAD and MAP3K7/TAK1 dependent pathways leading to NF-kappa-B and JNK activation. Acts as an important regulator of innate immune signaling via regulation of Nodlike receptors (NLRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Acts as a positive regulator of Wnt signaling and ubiquitinates TLE1, TLE2, TLE3, TLE4 and AES. Ubiquitination of TLE3 results in inhibition of its interaction with TCF7L2/TCF4 thereby allowing efficient recruitment and binding of the transcriptional coactivator beta- catenin to TCF7L2/TCF4 that is required to initiate a Wnt-specific transcriptional program. [The UniProt Consortium]