Pellino proteins are more than scaffold proteins in TLR/IL-1R signalling: a role as novel RING E3-ubiquitin-ligases.
Members of the Toll-like receptor (TLR) and IL-1 receptor (IL-1R) family initiate signalling pathways that shape innate immunity. Pellino proteins have recently been implicated as evolutionary conserved scaffold proteins in TLR/IL-1R signalling leading to nuclear factor-kappaB and mitogen activated protein kinase-dependent gene expression. We found that Pellino proteins contain a new RING-like motif. Because RING motifs are a feature of a subclass of E3-ubiquitin-ligases that target specific proteins for ubiquitination, we suggest that Pellino proteins are involved in TLR/IL-1R signalling not only as scaffold proteins but also as RING E3-ubiquitin-ligases. In support of this hypothesis we show that Pellino proteins induce IRAK-1 polyubiquitination in a RING-dependent manner. We further propose a model in which Pellino-mediated IRAK-1 polyubiquitination regulates TLR/IL-1R signalling.
Schauvliege
Reinout
R
Department for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology (VIB)--Ghent University, Technologiepark 927, B-9052 Ghent (Zwijnaarde), Belgium.
Janssens
Sophie
S
Beyaert
Rudi
R
D002460:Cell Line; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D053592:Interleukin-1 Receptor-Associated Kinases; D017346:Protein Serine-Threonine Kinases