Schauvliege Reinout, Janssens Sophie, Beyaert Rudi
Unit of Molecular Signal Transduction in Inflammation, Department for Molecular Biomedical Research, VIB, Ghent, Belgium.
J Cell Mol Med. 2007 May-Jun;11(3):453-61. doi: 10.1111/j.1582-4934.2007.00040.x.
Members of the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) family play important roles in immunity and inflammation. They initiate common intracellular signalling cascades leading to the activation of nuclear factor-?B (NF-?B) and other transcription factors that stimulate the expression of a variety of genes that shape an appropriate immune response. TLR/IL-1R signalling involves multiple proteinprotein interactions, but the mechanisms that regulate these interactions are still largely unclear. In this context, Pellino proteins have been suggested to function as evolutionary conserved scaffold proteins in TLR/IL-1R signalling. However, recently Pellino proteins were also proposed to function as novel ubiquitin ligases for IL-1R associated kinase 1 (IRAK-1). Here we review our current knowledge on the expression, biological role and mechanism of action of Pellino proteins in TLR/IL-1R-induced signalling.
Toll样受体(TLR)家族和白细胞介素-1受体(IL-1R)家族的成员在免疫和炎症中发挥着重要作用。它们启动共同的细胞内信号级联反应,导致核因子-κB(NF-κB)和其他转录因子的激活,这些转录因子刺激多种基因的表达,从而形成适当的免疫反应。TLR/IL-1R信号传导涉及多种蛋白质-蛋白质相互作用,但调节这些相互作用的机制仍不清楚。在这种情况下,Pellino蛋白被认为在TLR/IL-1R信号传导中作为进化保守的支架蛋白发挥作用。然而,最近Pellino蛋白也被提出作为白细胞介素-1受体相关激酶1(IRAK-1)的新型泛素连接酶发挥作用。在此,我们综述了目前关于Pellino蛋白在TLR/IL-1R诱导的信号传导中的表达、生物学作用和作用机制的知识。