RAIDD is a new 'death' adaptor molecule

Nature. 1997 Jan 2;385(6611):86-9. doi: 10.1038/385086a0.


The effector arm of the cell-death pathway is composed of cysteine proteases belonging to the ICE/CED-3 family. In metazoan cells these exist as inactive polypeptide precursors (zymogens), each composed of a prodomain, which is cleaved to activate the protease, and a large and small catalytic subunit. The coupling of these 'death' proteases to signalling pathways is probably mediated by adaptor molecules that contain protein-protein interaction motifs such as the death domain. Here we describe such an adaptor molecule, RAIDD, which has an unusual bipartite architecture comprising a carboxy-terminal death domain that binds to the homologous domain in RIP, a serine/threonine kinase component of the death pathway. The amino-terminal domain is surprisingly homologous with the sequence of the prodomain of two ICE/CED-3 family members, human ICH-1 (ref. 5) and Caenorhabditis elegans CED-3 (ref. 6). This similar region mediates the binding of RAIDD to ICH-1 and CED-3, serving as a direct link to the death proteases, indicating that the prodomain may, through homophilic interactions, determine the specificity of binding of ICE/CED-3 zymogens to regulatory adaptor molecules. Finally, alternations in the sequence of the N-terminal domain that are equivalent to inactivating mutations in the C. elegans ced-3 gene prevent homophilic binding, highlighting the potentially primordial nature of this interaction.

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD / metabolism
  • Apoptosis*
  • Caenorhabditis elegans Proteins
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Caspase 2
  • Caspases*
  • Cell Line
  • Helminth Proteins / metabolism
  • Humans
  • Molecular Sequence Data
  • Mutagenesis
  • Protein Binding
  • Proteins / metabolism
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Tumor Necrosis Factor, Type I
  • Sequence Homology, Amino Acid
  • Tissue Distribution
  • Transfection
  • Tumor Cells, Cultured


  • Antigens, CD
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Helminth Proteins
  • Proteins
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Caspase 2
  • Caspases
  • ced-3 protein, C elegans

Associated data

  • GENBANK/U79115