Molecular mechanisms of non-apoptotic CD95 signalling

• Applicant: Dr. Daniela Siegmund
• Subject Area: Cell Biology
• Term: from 2006 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 25555514

CD95 is the prototypic death receptor and has mainly attracted attention due to its apoptosis inducing capabilities. However, in recent years, several apoptosis-independent functions of CD95 became apparent. The molecular mechanisms of apoptotic CD95 signalling are comparably well understood, but those involved in non-apoptotic CD95 signalling are poorly defined. We have just demonstrated that CD95 activates NFxB via a pathway involving the CD95 associated proteins RIP, FADD and caspase-8 when apoptosis is blocked downstream of the CD95 signalling complex. Further, we found in the same experimental model CD95- induced activation of JNK, p38 and ERK. To gain a better understanding of the molecular basis of non-apoptotic CD95 signalling, we want to identify in this project proteins that are involved in CD95-mediated activation of the various MAP kinase cascades and the NFicB pathway. In particular, we want to study how signalling intermediates related to non-apoptotic CD95 signalling organize in CD95-associated and cytoplasmic protein complexes. The possible role of protein modification (phosphorylation, ubiquitination) of signalling intermediates for non-apoptotic signalling will also be addressed.

• DFG Programme: Research Grants