ICEBERG Background Information ICEBERG is a member of the death-domain-fold superfamily that is induced by proinflammatory stimuli. Primarily expressed in the heart and placenta, ICEBERG inhibits the generation of IL-1 beta which blocks apoptosis during an inflammatory stimulus. ICEBERG inhibits IL-1 beta by associating with caspase-1, thereby preventing caspase-1 from interacting with the pro-apoptotic protein RIP2. The association of ICEBERG with caspase-1 is facilitated by the charge-charge interactions between the prodomain of caspase-1 and the surface charge of ICEBERG. The association of caspase-1 with RIP2 will inhibit apoptosis by generating IL-1 beta. However, the association of caspase-1, which serves both pro and antiapoptotic roles, with ICEBERG induces apoptosis by inhibiting the generation of IL-1 beta.
