RAIDD is a new 'death' adaptor molecule

Article

关键词: PROGRAMMED CELL-DEATH;    C-ELEGANS;    PROTEIN;    GENE;    INTERACTS;    APOPTOSIS;    ENCODES;    DOMAIN;    FAS;   

DOI  :  10.1038/385086a0

来源: SCIE

【 摘 要 】

THE effector arm of the the cell-death pathway is composed of cysteine proteases belonging to the ICE/CED-3 family(1,2). 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(1). Were 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(3,4). 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(7,8) prevent homophilic binding, highlighting the potentially primordial nature of this interaction.

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