Human CARD4 Protein Is a Novel CED-4/Apaf-1 Cell Death Family Member That Activates NF-κB

Abstract

The nematode CED-4 protein and its human homolog Apaf-1 play a central role in apoptosis by functioning as direct activators of death-inducing caspases. A novel human CED-4/Apaf-1 family member called CARD4 was identified that has a domain structure strikingly similar to the cytoplasmic, receptor-like proteins that mediate disease resistance in plants. CARD4 interacted with the serine-threonine kinase RICK and potently induced NF-B activity through TRAF-6 and NIK signaling molecules. In addition, coexpression of CARD4 augmented caspase-9-induced apoptosis. Thus, CARD4 coordinates downstream NF-B and apoptotic signaling pathways and may be a component of the host innate immune response.

Cloning of two rainbow trout nucleotide-binding oligomerization domain containing 2 (NOD2) splice variants and functional characterization of the NOD2 effector domains

“…[25,47e51]. In humans, members of NLRs can coordinate caspaseinduced apoptotic signaling pathways [52,53]. Our previous study showed that overexpression of zebrafish NOD2 had no effect on cell viability when expressed alone.…”

Failure of Bcl-2 family members to interact with Apaf-1 in normal and apoptotic cells

“…Thus, instead of being sequestered to membraneassociated Bcl-2 or Bcl-x L , Apaf-1 seems to constitutively reside in the cytoplasm to await the release of cytochrome c for the activation of caspase-9. A novel CED-4 homolog, named Nod1/CARD4 42,43 has recently been identified, and it will be interesting to determine whether it fulfills the criteria to form an apoptosome with Bcl-2 or Bcl-x L . Based on the findings that Bcl-2 and Bcl-x L prevent the release of cytochrome c, it is expected that these proteins bind to and inhibit a CED-4 homolog that functions upstream of mitochondria to initiate the release of cytochrome c and other apoptogenic factors.…”

Molecular characterization and expression analysis of nuclear oligomerization domain proteins NOD1 and NOD2 in grass carp Ctenopharyngodon idella

“…NOD1 and NOD2 have been cloned from mammals including human beings [14], mice [15] and porcine [16,17]. An examination of the zebrafish genome suggests that mammalian NOD1 and NOD2 orthologs also existed in fish [18,19].…”