mE10, a novel caspase recruitment domain-containing proapoptotic molecule.
Apoptotic signaling is mediated by homophilic interactions between conserved domains present in components of the death pathway. The death domain, death effector domain, and caspase recruitment domain (CARD) are examples of such interaction motifs. We have identified a novel mammalian CARD-containing adaptor molecule termed mE10 (mammalian E10). The N-terminal CARD of mE10 exhibits significant homology (47% identity and 64% similarity) to the CARD of a gene from Equine Herpesvirus type 2. The C-terminal region is unique. Overexpression of mE10 in MCF-7 human breast carcinoma cells induces apoptosis. Mutational analysis indicates that CARD-mediated mE10 oligomerization is essential for killing activity. The C terminus of mE10 bound to the zymogen form of caspase-9 and promoted its processing to the active dimeric species. Taken together, these data suggest a model where autoproteolytic activation of pro-caspase-9 is mediated by mE10-induced oligomerization.
Yan
M
M
Department of Molecular Oncology, Genentech, Inc., South San Francisco, California 94080, USA.
Lee
J
J
Schilbach
S
S
Goddard
A
A
Dixit
V
V
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1; D000074018:B-Cell CLL-Lymphoma 10 Protein; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D016415:Sequence Alignment
C506592:APAF1 protein, human; D048868:Adaptor Proteins, Signal Transducing; C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; C488088:Bcl10 protein, mouse; D002352:Carrier Proteins; D009363:Neoplasm Proteins; D011506:Proteins; C505407:CASP3 protein, human; C506433:CASP9 protein, human; C505409:Casp3 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases