RIP3, a novel apoptosis-inducing kinase

RIPS is a novel gene product containing a N-terminal kinase domain that shares extensive homology with the corresponding domain in RIP (receptor-interacting protein) and RIPE. Unlike RIP, which has a C-terminal death domain, and RIPE, which has a C-terminal caspase activation and recruitment domain, RIPS has a unique C terminus. RIPS binds RIP through its unique C-terminal segment and by virtue of this interaction is recruited to the tumor necrosis factor (TNF) receptor-1 signaling complex. Previous studies have shown that RIP mediates TNF-induced activation of the anti-apoptotic NF-KB pathway. RIPS, however, attenuates both RIP and TNF receptor-1-induced NF-KB activation. Overexpression studies revealed RIPS to be a potent inducer of apoptosis, capable of selectively binding to large prodomain initiator caspases.