| First Author | Mikula M | Year | 2001 |
| Journal | EMBO J | Volume | 20 |
| Issue | 8 | Pages | 1952-62 |
| PubMed ID | 11296228 | Mgi Jnum | J:69056 |
| Mgi Id | MGI:1933943 | Doi | 10.1093/emboj/20.8.1952 |
| Citation | Mikula M, et al. (2001) Embryonic lethality and fetal liver apoptosis in mice lacking the c-raf-1 gene. EMBO J 20(8):1952-62 |
| abstractText | The Raf kinases play a key role in relaying signals elicited by mitogens or oncogenes. Here, we report that c-raf-1(-/-) embryos are growth retarded and die at midgestation with anomalies in the placenta and in the fetal liver. Although hepatoblast proliferation does not appear to be impaired, c-raf-1(-/-) fetal livers are hypocellular and contain numerous apoptotic cells. Similarly, the poor proliferation of Raf-1(-/-) fibroblasts and hematopoietic cells cultivated in vitro is due to an increase in the apoptotic index of these cultures rather than to a cell cycle defect. Furthermore, Raf-1- deficient fibroblasts are more sensitive than wild- type cells to specific apoptotic stimuli, such as actinomycin D or Fas activation, but not to tumor necrosis factor-alpha. MEK/ERK activation is normal in Raf-1-deficient cells and embryos, and is probably mediated by B-RAF. These results indicate that the essential function of Raf-1 is to counteract apoptosis rather than to promote proliferation, and that effectors distinct from the MEK/ERK cascade must mediate the anti-apoptotic function of Raf-1. |
