title: Molecular and physiological roles of Pellino E3 ubiquitin ligases in immunity.
abstract: The sensing of foreign agents by the innate and adaptive immune system triggers complex signal transduction cascades that culminate in expression of gene patterns that facilitate host protection from the invading agent. Post-translational modification of intracellular signaling proteins in these pathways is a key regulatory mechanism with ubiquitination being one of the important processes that controls levels and activities of signaling molecules. E3 ubiquitin ligases are the determining enzymes in dictating the ubiquitination status of individual proteins. Among these hundred E3 ubiquitin ligases are a family of Pellino proteins that are emerging to be important players in immunity and beyond. Herein, we review the roles of the Pellino E3 ubiquitin ligases in innate and adaptive immunity. We discuss their early discovery and characterization and how this has been aided by the highly conserved nature of innate immune signaling across evolution. We describe the molecular roles of Pellino proteins in immune signaling with particular emphasis on their involvement in pathogen recognition receptor (PRR) signaling. The growing appreciation of the importance of Pellino proteins in a wide range of immune-mediated diseases are also evaluated.
authors.affiliation: Institute of Immunology, Department of Biology, National University of Ireland Maynooth, Maynooth, Ireland.
authors.forename: Fiachra
authors.initials: F
authors.lastname: Humphries
authors.affiliation: Institute of Immunology, Department of Biology, National University of Ireland Maynooth, Maynooth, Ireland.|Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Northern Ireland, UK.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Moynagh
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D006801:Humans; D007113:Immunity, Innate; D009687:Nuclear Proteins / Q000378:metabolism*; D051192:Receptors, Pattern Recognition / Q000378:metabolism*; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D009687:Nuclear Proteins; D051192:Receptors, Pattern Recognition; C485959:PELI1 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: NOD-like receptors; Pellino E3 ubiquitin ligases; Toll-like receptors; inflammation; innate immunity; ubiquitination