Pellino Proteins: Novel Players in TLR and IL‐1R Signalling

Introduction Pellino proteins are extremely well conserved during evolution Genomic organisation and protein structure of Pellino Pellino proteins interact with key mediators in TLR/IL‐1R‐induced signalling pathways Role of Pellino proteins in TLR/IL‐1R signalling to NF‐κB and MAPK Perspectives Abstract 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‐κB (NF‐κB) 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 protein–protein 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.