| First Author | Imai Y | Year | 1999 |
| Journal | Nature | Volume | 398 |
| Issue | 6730 | Pages | 777-85 |
| PubMed ID | 10235259 | Mgi Jnum | J:55798 |
| Mgi Id | MGI:1347587 | Doi | 10.1038/19709 |
| Citation | Imai Y, et al. (1999) The CED-4-homologous protein FLASH is involved in Fas-mediated activation of caspase-8 during apoptosis [see comments] [published erratum appears in Nature 1999 Jul 1;400(6739):89]. Nature 398(6730):777-85 |
| abstractText | Fas is a cell-surface receptor molecule that relays apoptotic (cell death) signals into cells. When Fas is activated by binding of its ligand, the proteolytic protein caspase-8 is recruited to a signalling complex known as DISC by binding to a Fas-associated adapter protein. A large new protein, FLASH, has now been identified by cloning of its complementary DNA. This protein contains a motif with oligomerizing activity whose sequence is similar to that of the Caenorhabditis elegans protein CED-4, and another domain (DRD domain) that interacts with a death-effector domain in caspase-8 or in the adapter protein. Stimulated Fas binds FLASH, so FLASH is probably a component of the DISC signalling complex. Transient expression of FLASH activates caspase-8, whereas overexpression of a truncated form of FLASH containing only one of its DRD or CED-4-like domains does not allow activation of caspase-8 and Fas-mediated apoptosis to occur. Overexpression of full-length FLASH blocks the anti-apoptotic effect of the adenovirus protein E1B19K. FLASH is therefore necessary for the activation of caspase-8 in Fas-mediated apoptosis. |
