PMID- 10187815 OWN - NLM STAT- MEDLINE DCOM- 19990503 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 274 IP - 15 DP - 1999 Apr 9 TI - mE10, a novel caspase recruitment domain-containing proapoptotic molecule. PG - 10287-92 AB - 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. FAU - Yan, M AU - Yan M AD - Department of Molecular Oncology, Genentech, Inc., South San Francisco, California 94080, USA. FAU - Lee, J AU - Lee J FAU - Schilbach, S AU - Schilbach S FAU - Goddard, A AU - Goddard A FAU - Dixit, V AU - Dixit V LA - eng SI - GENBANK/AA119259 SI - GENBANK/AA455396 SI - GENBANK/AF127386 SI - GENBANK/AF127387 SI - GENBANK/W47752 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (APAF1 protein, human) RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Apaf1 protein, mouse) RN - 0 (Apoptotic Protease-Activating Factor 1) RN - 0 (B-Cell CLL-Lymphoma 10 Protein) RN - 0 (BCL10 protein, human) RN - 0 (Bcl10 protein, mouse) RN - 0 (Carrier Proteins) RN - 0 (Neoplasm Proteins) RN - 0 (Proteins) RN - EC 3.4.22.- (CASP3 protein, human) RN - EC 3.4.22.- (CASP9 protein, human) RN - EC 3.4.22.- (Casp3 protein, mouse) RN - EC 3.4.22.- (Casp9 protein, mouse) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.22.- (Caspase 9) RN - EC 3.4.22.- (Caspases) SB - IM MH - *Adaptor Proteins, Signal Transducing MH - Amino Acid Sequence MH - Animals MH - *Apoptosis MH - Apoptotic Protease-Activating Factor 1 MH - B-Cell CLL-Lymphoma 10 Protein MH - Binding Sites MH - Carrier Proteins/genetics/*metabolism MH - Caspase 3 MH - Caspase 9 MH - Caspases/*metabolism MH - Cell Line MH - Cloning, Molecular MH - Enzyme Activation MH - Humans MH - Mice MH - Molecular Sequence Data MH - Neoplasm Proteins/genetics/*metabolism MH - Proteins/metabolism MH - Sequence Alignment EDAT- 1999/04/03 00:00 MHDA- 1999/04/03 00:01 CRDT- 1999/04/03 00:00 PHST- 1999/04/03 00:00 [pubmed] PHST- 1999/04/03 00:01 [medline] PHST- 1999/04/03 00:00 [entrez] AID - 10.1074/jbc.274.15.10287 [doi] AID - S0021-9258(19)73713-2 [pii] PST - ppublish SO - J Biol Chem. 1999 Apr 9;274(15):10287-92. doi: 10.1074/jbc.274.15.10287.