Nod1, an Apaf-1-like activator of caspase-9 and nuclear factor-kappaB

Ced-4 and Apaf-1 belong to a major class of Apoptosis regulators that contain caspase-recruitment (CARD) and nucleotide-binding oligomerization domains. NOD1, a protein with an NH2-terminal CARD-linked to a nucleotide-binding domain and a COOH-terminal segment with multiple leucine-rich repeats, was identified. Nod-1 was found to bind to multiple caspases with long prodomains, but specifically activated caspase-9 and promoted caspase-9-induced Apoptosis. As reported for Apaf-1, NOD1 required both the CARD and P-loop for function. Unlike Apaf-1, NOD1 induced activation of nuclear factor-kappa-B (NF-kappaB) and bound RICK, a CARD-containing kinase that also induces NF-kappaB activation. NOD1 mutants inhibited NF-kappaB activity induced by RICK, but not that resulting from tumor necrosis factor-alpha stimulation. Thus, NOD1 is a leucine-rich repeat-containing Apaf-1-like molecule that can regulate both Apoptosis and NF-kappaB activation pathways.