TY  - JOUR
A1  - Jesenberger, Veronika
A1  - Procyk, Katarzyna
A1  - Rüth, Jochen
A1  - Schreiber, Martin
A1  - Theussl, Hans Christian
A1  - Wagner, Erwin
A1  - Baccarini, Manuela
T1  - Protective Role of Raf-1 in Salmonella-Induced Macrophage Apoptosis
JF  - J Exp Med.
N2  - Invasive Salmonella induces macrophage apoptosis via the activation of caspase-1 by the bacterial protein SipB. Here we show that infection of macrophages with Salmonella causes the activation and degradation of Raf-1, an important intermediate in macrophage proliferation and activation. Raf-1 degradation is SipB- and caspase-1–dependent, and is prevented by proteasome inhibitors. To study the functional significance of Raf-1 in this process, the c-raf-1 gene was inactivated by Cre-loxP–mediated recombination in vivo. Macrophages lacking c-raf-1 are hypersensitive towards pathogen-induced apoptosis. Surprisingly, activation of the antiapoptotic mitogen-activated protein kinase kinase (MEK)/extracellular signal–regulated kinase (ERK) and nuclear factor κB pathways is normal in Raf-1–deficient macrophages, and mitochondrial fragility is not increased. Instead, pathogen-mediated activation of caspase-1 is enhanced selectively, implying that Raf-1 antagonizes stimulus-induced caspase-1 activation and apoptosis.
KW  - Salmonella-Induced Macrophage Apoptosis
KW  - Raf-1 pathway
KW  - Molecular Cell Biology
Y1  - 2020
U6  - http://dx.doi.org/10.1084/jem.193.3.353
VL  - 2001
IS  - 193(3)
SP  - 353
EP  - 364
ER  -