The Role of RIP2 in activation of NF-kappaB and regulation of XIAP-induced metastasis

结直肠癌是西欧肿瘤相关死亡的第二大原因。近年来，一组抗凋亡蛋白--凋亡抑制蛋白（inhibitor of apoptosis protein，IAP）家族因能抑制细胞凋亡诱导的半胱氨酸天冬氨酸蛋白酶（caspase）而引起人们的关注。XIAP是该家族中最知名的成员之一，其特征在于其抗凋亡特性以及其作为转录因子NF-κ B的激活剂的功能。因此，NF-κ B诱导的信号通路在肿瘤的发生和转移中起着重要的作用，本课题旨在阐明XIAP诱导的NF-κ B活化在结直肠癌中的分子机制。在这种情况下，中心目标之一是显示衔接蛋白RIP 2和TAB 1与XIAP诱导的NF-κ B活化的相关性。因此，RIP 2、TAB 1和XIAP之间的分子和功能相互作用的这些数据可能为结直肠癌的治疗策略提供新的见解。

Colorectal Cancer is the second leading cause of tumor related deaths in western europe. Independently of diagnostic tools and operative strategies, even against metastatic disease, the main dilemma remains the development of tumor recurrence and metastasizing disease, of which the molecular mechanism are not completely understood.Recently, a group of antiapototic proteins, the inhibitor of apoptosis protein (IAP) family, attracted attention due to their inhibition of cell death inducing caspases. XIAP is one of the best known members of this family characterized by its antiapoptotic properties as well as its function as activator of the transcription factor NF-kappaB. Thus it is known, that NF-kappaB induced signaling pathways play a crucial role in tumorigenesis and metastasis.Aim of the presented project is to elucidate the molecular mechanisms of XIAP-induced NF-kappaB activation in tumor progression in colorectal cancers. In this context, one of the central aims is to show the relevance of both adaptor proteins RIP2 and TAB1 for XIAP-induced NF-kappaB activation. Thus, these data of the molecular and functional interaction between RIP2, TAB1 and XIAP might provide new insights for therapeutical strategies in colorectal cancer.