Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins

To identify proteins that bind mammalian IAP homolog A (MIHA, also known as XIAP), we used coimmunoprecipitation and 2D immobilized pH gradient/SDS PA GE, followed by electrospray ionization tandem mass spectrometry. DIABLO (d irect IAP binding protein with low pi) is a novel protein that can bind MIH A and can also interact with MIHB and MIHC and the baculoviral IAP, OpIAP. The N-terminally processed, IAP-interacting form of DIABLO is concentrated in membrane fractions in healthy cells but released into the MIHA-containin g cytosolic fractions upon UV irradiation. As transfection of cells with DI ABLO was able to counter the protection afforded by MIHA against UV irradia tion, DIABLO may promote apoptosis by binding to IAPs and preventing them f rom inhibiting caspases.