Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Mikula, M; Schreiber, M; Husak, Z; Kucerova, L; Rüth, J; Wieser, R; Zatloukal, K; Beug, H; Wagner, EF; Baccarini, M.
Embryonic lethality and fetal liver apoptosis in mice lacking the c-raf-1 gene.
EMBO J. 2001; 20(8):1952-1962
Doi: 10.1093/emboj/20.8.1952
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- Co-Autor*innen der Med Uni Graz
- Zatloukal Kurt
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Apoptosis -
- Cell Cycle -
- Fibroblasts - cytology
- Genes, Lethal - cytology
- Hematopoiesis - genetics
- Hematopoietic Stem Cells - genetics
- Homozygote - genetics
- I-kappa B Proteins - metabolism
- Liver - embryology
- Mice - embryology
- Mice, Mutant Strains - embryology
- Mitogen-Activated Protein Kinases - metabolism
- Mutagenesis - metabolism
- Phenotype - metabolism
- Proto-Oncogene Proteins c-raf - genetics
- Signal Transduction - genetics
- Find related publications in this database (Keywords)
- apoptosis
- development
- gene inactivation
- MAP kinase
- proliferation