RIP3, a Novel Apoptosis-inducing Kinase

• Published in: The Journal of biological chemistry 1999-06, Vol.274 (24), p.16871-16875
• Main Authors: Sun, X, Lee, J, Navas, T, Baldwin, D T, Stewart, T A, Dixit, V M
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Antigens, CD - metabolism; Apoptosis; Caspases - metabolism; Cloning, Molecular; Humans; Molecular Sequence Data; NF-kappa B - metabolism; Protein Binding; Protein Kinases - genetics; Protein Kinases - metabolism; Protein-Serine-Threonine Kinases; Proteins - metabolism; Receptor-Interacting Protein Serine-Threonine Kinase 2; Receptor-Interacting Protein Serine-Threonine Kinases; Receptors, Tumor Necrosis Factor - metabolism; Receptors, Tumor Necrosis Factor, Type I; Recombinant Proteins - metabolism; Sequence Analysis; Sequence Homology, Amino Acid; Signal Transduction
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.274.24.16871

RIP3 is a novel gene product containing a N-terminal kinase domain that shares extensive homology with the corresponding domain in RIP ( r eceptor- i nteracting p rotein) and RIP2. Unlike RIP, which has a C-terminal death domain, and RIP2, which has a C-terminal caspase activation and recruitment domain, RIP3 has a unique C terminus. RIP3 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-κB pathway. RIP3, however, attenuates both RIP and TNF receptor-1-induced NF-κB activation. Overexpression studies revealed RIP3 to be a potent inducer of apoptosis, capable of selectively binding to large prodomain initiator caspases.