Identification of a cell protein (FIP-3) as a modulator of NF-kappa B activity and as a target of an adenovirus inhibitor of tumor necrosis factor alpha-induced apoptosis

FIP-3 (14.7K interacting protein) was discovered during a search for cell p roteins that could interact with an adenovirus protein (Ad E3-14.7K) that h ad been shown to prevent tumor necrosis factor (TNF)-alpha-induced cytolysi s, FIP-3, which contains leucine zippers and a zinc finger domain, inhibits both basal and induced transcriptional activity of NF-kappa B and causes a late-appearing apoptosis with unique morphologic manifestations. Ad E3-14. 7K can partially reverse apoptotic death induced by FIP-3, FIP-3 also was s hown to bind to other cell proteins, RIP and NIK, which previously had been described as essential components of TNF-alpha-induced NF-kappa B activati on. In addition, FIP-3 inhibited activation of NF-kappa B induced by TNF-al pha, the TNFR-1 receptor, RIP, NIK, and IKK beta, as well as basal levels o f endogenous NF-kappa B in 293 cells. Because the activation of NF-kappa B has been shown to inhibit apoptosis, FIP-3 appears both to activate a cell- death pathway and to inhibit an NF-kappa B-dependent survival mechanism.