Scientific background: |
XAF1 also called XIAP-associated factor 1?antagonizes the anticaspase activity of XIAP and may be important in mediating apoptosis resistance in cancer cells. By genomic sequence analysis, the XAF1 gene contains 7 exons spanning 18 kb. Southern blot analysis suggested that XAF1 is a single-copy gene. The XAF1 gene is mapped on 17p13.1. Fluorescence microscopy demonstrated nuclear expression of XAF1, in contrast to the cytoplasmic expression of XIAP. Functional analysis indicated that XAF1 reverses the XIAP-mediated inhibition of CASP3 and its protection against apoptosis. Northern blot analysis detected wide expression of 3.9-, 4.5-, 6.0-, and 7.0-kb XAF1 transcripts, with highest levels in heart and ovary and lowest levels in brain and testis. Antisense experiments determined that loss of XAF1 expression enhances resistance to apoptosis. Alteration in XAF1 and XIAP RNA expression levels may lead to increased apoptotic resistance and proliferation due to unregulated XIAP function in cancer cells. |
References: |
1.Fong, W. G., Liston, P., Rajcan-Separovic, E., St. Jean, M., Craig, C., Korneluk, R. G. Expression and genetic analysis of XIAP-associated factor 1 (XAF1) in cancer cell lines. Genomics 70: 113-122, 2000.
2.Liston, P., Fong, W. G., Kelly, N. L., Toji, S., Miyazaki, T., Conte, D., Tamai, K., Craig, C. G., McBurney, M. W., Korneluk, R. G. Identification of XAF1 as an antagonist of XIAP anti-caspase activity. Nature Cell Biol. 3: 128-133, 2001.
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