Pellino proteins are more than scaffold proteins in TLR/IL-1R signalling: a role as novel RING E3-ubiquitin-ligases

FEBS Lett. 2006 Aug 21;580(19):4697-702. doi: 10.1016/j.febslet.2006.07.046. Epub 2006 Jul 24.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Humans
  • Interleukin-1 Receptor-Associated Kinases
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Nuclear Proteins / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptors, Interleukin-1 / metabolism*
  • Signal Transduction*
  • Toll-Like Receptors / metabolism*
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Receptors, Interleukin-1
  • Toll-Like Receptors
  • Ubiquitin
  • Ubiquitin-Protein Ligases
  • Interleukin-1 Receptor-Associated Kinases
  • Protein-Serine-Threonine Kinases