Molecular mechanisms of non-apoptotic CD95 signalling

CD95是典型的死亡受体，主要因其诱导细胞凋亡的能力而受到关注。然而，近年来，CD95的一些与凋亡无关的功能变得明显。CD95细胞凋亡信号传导的分子机制已经被很好地理解，但那些参与非凋亡CD95信号传导的分子机制还不清楚。我们刚刚证明，当CD95信号复合物的下游细胞凋亡被阻断时，CD95通过一条涉及CD95相关蛋白RIP、FADD和caspase-8的途径激活NFxB。此外，在相同的实验模型中，我们发现CD95诱导JNK、p38和ERK活化。为了更好地了解非凋亡性CD95信号的分子基础，我们希望在本项目中确定参与CD95介导的各种MAP激酶级联和NFicB通路激活的蛋白。特别是，我们想要研究与非凋亡CD95信号相关的信号中间体如何在CD95相关和细胞质蛋白复合物中组织。蛋白质修饰（磷酸化，泛素化）在非凋亡信号传导中的可能作用也将被解决。

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.