Table of Contents
Journal of Signal Transduction
Volume 2011 (2011), Article ID 834948, 12 pages
Research Article

Raf-1 Activation Prevents Caspase 9 Processing Downstream of Apoptosome Formation

Institute of Developmental Biology and Cancer, CNRS UMR6543, A. Lacassagne Center, University of Nice Sophia-Antipolis, 33 Avenue Valombrose, 06189 Nice, France

Received 30 July 2010; Revised 16 September 2010; Accepted 21 September 2010

Academic Editor: Alakananda Basu

Copyright © 2011 Sébastien Cagnol et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


In many cell types, growth factor removal induces the release of cytochrome-c from mitochondria that leads to activation of caspase-9 in the apoptosome complex. Here, we show that sustained stimulation of the Raf-1/MAPK1,3 pathway prevents caspase-9 activation induced by serum depletion in CCL39/ Δ Raf-1:ER fibroblasts. The protective effect mediated by Raf-1 is sensitive to MEK inhibition that is sufficient to induce caspase-9 cleavage in exponentially growing cells. Raf-1 activation does not inhibit the release of cytochrome-c from mitochondria while preventing caspase-9 activation. Gel filtration chromatography analysis of apoptosome formation in cells shows that Raf-1/MAPK1,3 activation does not interfere with APAF-1 oligomerization and recruitment of caspase 9. Raf-1-mediated caspase-9 inhibition is sensitive to emetine, indicating that the protective mechanism requires protein synthesis. However, the Raf/MAPK1,3 pathway does not regulate XIAP. Taken together, these results indicate that the Raf-1/MAPK1,3 pathway controls an apoptosis regulator that prevents caspase-9 activation in the apoptosome complex.