XIAP : X-linked inhibitor of apoptosis

Description

The XIAP (X-linked inhibitor of apoptosis) is a protein-coding gene located on chromosome X.

The XIAP gene provides instructions for making a protein that is found in many types of cells, including immune cells. It helps protect these cells from self-destructing (undergoing apoptosis) by blocking (inhibiting) the action of certain enzymes called caspases, which are necessary for apoptosis. Specifically, the XIAP protein inhibits caspase enzymes 3, 7, and 9. The XIAP protein also plays a role in several other signaling pathways that are involved in various functions in the body.

XIAP is a multifunctional protein that plays crucial roles in regulating various cellular processes, including apoptosis, inflammation, immunity, copper homeostasis, cell proliferation, and metastasis. It directly inhibits caspase activity, primarily caspase-3, -7, and -9, by binding to their active sites and blocking substrate access. XIAP also functions as an E3 ubiquitin-protein ligase, regulating NF-κB signaling by targeting specific proteins for ubiquitination, including RIPK1, RIPK2, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS, PTEN, and BIRC5/survivin. It acts as a key regulator of innate immunity by promoting Lys-63-linked polyubiquitination of RIPK2 downstream of NOD1 and NOD2, converting RIPK2 into a scaffold protein for downstream effectors and activating NF-κB and MAP kinase signaling. XIAP also regulates the BMP signaling pathway, SMAD, and MAP3K7/TAK1-dependent pathways, leading to NF-κB and JNK activation. Furthermore, XIAP plays a role in copper homeostasis by ubiquitinating and promoting the proteasomal degradation of COMMD1. It can also function as an E3 ubiquitin-protein ligase in the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. XIAP ubiquitinates and mediates the proteasomal degradation of BCL2 in response to apoptosis. It protects cells from spontaneous ripoptosome formation, a complex that can kill cancer cells, by ubiquitinating RIPK1 and CASP8. XIAP acts as a positive regulator of Wnt signaling, ubiquitinating TLE1, TLE2, TLE3, TLE4, and AES, ultimately leading to the inhibition of TLE3 interaction with TCF7L2/TCF4 and facilitating the recruitment of beta-catenin to initiate Wnt-specific transcription.

XIAP is also known as API3, BIRC4, IAP-3, ILP1, MIHA, XLP2, hIAP-3, hIAP3.

Associated Diseases

• Lymphoproliferative syndrome, X-linked, 2
• Lymphoproliferative syndrome, X-linked, 1
• X-linked lymphoproliferative disease