Molecular mechanisms of non-apoptotic CD95 signalling

非凋亡 CD95 信号传导的分子机制

• 批准号: 25555514
• 负责人: Dr. Daniela Siegmund
• 金额: --
• 依托单位: Abteilung für Molekulare Innere Medizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/25555514?language=en
• 关键词: Molecular; mechanisms; non; apoptotic; CD95

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.

CD95是典型的死亡受体，主要由于其诱导细胞凋亡的能力而引起人们的关注。然而，近年来，CD95的一些不依赖于细胞凋亡的功能变得明显起来。细胞凋亡性CD95信号传导的分子机制已被较好地理解，但涉及非凋亡性CD95信号传导的分子机制却知之甚少。我们刚刚证明，当CD95信号复合体下游的凋亡被阻断时，CD95通过涉及CD95相关蛋白RIP、FADD和caspase-8的途径激活NFxB。此外，在同一实验模型中，我们发现CD95诱导了JNK、p38和ERK的激活。为了更好地了解非凋亡性CD95信号的分子基础，我们希望在这个项目中识别参与CD95介导的各种MAP激酶级联反应和NFicB途径激活的蛋白质。特别是，我们想要研究与非凋亡性CD95信号相关的信号中间产物是如何在CD95相关和细胞质蛋白复合体中组织的。蛋白质修饰(磷酸化、泛素化)的信号中间产物对于非凋亡信号的可能作用也将被讨论。