Embryonic lethality and fetal liver apoptosis in mice lacking the c-raf-1 gene

Autor(en)

Mario Mikula, Martin Schreiber, Zvenislava Husak, Lucia Kucerova, Jochen Rüth, Rotraud Wieser, Kurt Zatloukal, Hartmut Beug, Erwin Friedrich Wagner, Manuela Baccarini

Abstrakt

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 wildtype cells to specific apoptotic stimuli, such as actinomycin D or Fas activation, but not to tumor necrosis factor-a. MEK/ERK activation is normal in Raf-l-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.

Organisation(en)

Department für Ernährungswissenschaften, Department für Biochemie und Zellbiologie

Externe Organisation(en)

Karl-Franzens-Universität Graz, Max F. Perutz Laboratories GmbH (MFPL), Medizinische Universität Wien, Medizinische Universität Graz

Journal

The EMBO Journal

Band

20

Seiten

1952-1962

Anzahl der Seiten

11

ISSN

0261-4189

Publikationsdatum

2001

Peer-reviewed

Ja

ÖFOS 2012

1060 Biologie

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/222cddb7-4ad3-4160-9941-2b4a5539a9ba