Inhibiting an Apoptosis Inhibitor

Science's STKE  13 Feb 2001:
Vol. 2001, Issue 69, pp. tw4
DOI: 10.1126/stke.2001.69.tw4

The inhibitors of apoptosis (IAPs) are endogenous inhibitors of caspases, enzymes that promote cell death. Liston et al. have now identified an inhibitor of X-linked IAP (XIAP) called XIAP-associated factor 1 (XAF1) in a yeast two-hybrid screen. Both proteins could be coimmunoprecipitated from lysates when overexpressed in cultured cells. Overexpression of XAF1 also caused the relocalization of endogenous XIAP from the nucleus to the cytoplasm. XAF1 both inhibited the anti-caspase activity of XIAP in vitro and suppressed the protective effects of XIAP in cells exposed to conditions that induce apoptosis. The authors propose that loss of XAF1 expression in cancer cells may enhance resistance to apoptosis.

P. Liston, W.G. Fong, N.L. Kelly, S. Toji, T. Miyazaki, D. Conte, K. Tamai, C.G. Craig, M.W. McBurney, R.G. Korneluk, Identification of XAF1 as an antagonist of XIAP anti-caspase activity. Nature Cell Biol. 3, 128-133 (2001). [Online Journal]