XIAP Associated Factor-1 (XAF-1) binds to XIAP, an inhibitor of caspases 3, 7, and 9, and triggers its relocation from the cytosol to the nucleus. Overexpression of XAF-1 results in the neutralization of XIAP’s ability to inhibit cell death. XAF-1 is normally expressed in all adult and fetal tissues but was found to be present in very low levels in a variety of cancer cell lines. In contrast, XIAP levels have been shown to be high in a majority of cell lines. Low XAF-1 and high basal expression of XIAP may therefore play a critical role in maintaining survival of cancer cell lines. Both IFN-a2 and IFN-b can induce XAF-1 mRNA in all cells examined but induction of XAF-1 protein (as observed by immunoblot analysis) was seen only in cell lines sensitive to the apoptotic effects of IFNs.
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