| RRC ID |
28678
|
| 著者 |
Sakamaki K, Takagi C, Kominami K, Sakata S, Yaoita Y, Kubota HY, Nozaki M, Yonehara S, Ueno N.
|
| タイトル |
The adaptor molecule FADD from Xenopus laevis demonstrates evolutionary conservation of its pro-apoptotic activity.
|
| ジャーナル |
Genes Cells
|
| Abstract |
FADD is an adaptor protein that transmits apoptotic signals from death receptors such as Fas to downstream initiator caspases in mammals. We have identified and characterized the Xenopus orthologue of mammalian FADD (xFADD). xFADD contains both a death effector domain (DED) and a death domain (DD) that are structurally homologous to those of mammalian FADD. We observed xFADD binding to Xenopus caspase-8 and caspase-10 as well as to human caspase-8 and Fas through interactions with their homophilic DED and DD domains. When over-expressed, xFADD was also able to induce apoptosis in wild-type mouse embryonic fibroblasts (MEF), but not in caspase-8-deficient MEF cells. In contrast, DED-deficient xFADD (xFADDdn) acted as a dominant-negative mutant and prevented Fas-mediated apoptosis in mammalian cell lines. These results indicate that xFADD transmits apoptotic signals from Fas to caspase-8. Furthermore, we found that transgenic animals expressing xFADD in the developing heart or eye under the control of tissue-specific promoters show abnormal phenotypes. Taken together, these results suggest that xFADD can substitute functionally for its mammalian homologue in death receptor-mediated apoptosis, and we suggest that xFADD functions as a pro-apoptotic adaptor molecule in frogs. Thus, the structural and functional similarities between xFADD and mammalian FADD provide evidence that the apoptotic pathways are evolutionally conserved across vertebrate species.
|
| 巻・号 |
9(12)
|
| ページ |
1249-64
|
| 公開日 |
2004-12-1
|
| DOI |
10.1111/j.1365-2443.2004.00802.x
|
| PII |
GTC802
|
| PMID |
15569156
|
| MeSH |
Adaptor Proteins, Signal Transducing / genetics*
Amino Acid Sequence
Animals
Apoptosis*
Arabidopsis Proteins / genetics*
Arabidopsis Proteins / metabolism
Base Sequence
Caspase 10
Caspase 8
Caspases / metabolism
Conserved Sequence
Evolution, Molecular*
Fatty Acid Desaturases / genetics*
Fatty Acid Desaturases / metabolism
Gene Expression
Humans
Mice
Molecular Sequence Data
Mutation
RNA, Messenger / metabolism
Sequence Alignment
Sequence Deletion
Signal Transduction
Xenopus Proteins / genetics*
Xenopus Proteins / metabolism
|
| IF |
1.655
|
| 引用数 |
17
|
|
WOS 分野
|
GENETICS & HEREDITY
CELL BIOLOGY
|
| リソース情報 |
| 遺伝子材料 |
pxlFADD (Xenopus FADD) (RDB08076) |
