Peli: a family of signal-responsive E3 ubiquitin ligases mediating TLR signaling and T-cell tolerance

Cell Mol Immunol. 2012 Mar;9(2):113-22. doi: 10.1038/cmi.2011.60. Epub 2012 Feb 6.


E3 ubiquitin ligases play a crucial role in regulating immune receptor signaling and modulating immune homeostasis and activation. One emerging family of such E3s is the Pelle-interacting (Peli) proteins, characterized by the presence of a cryptic forkhead-associated domain involved in substrate binding and an atypical RING domain mediating formation of both lysine (K) 63- and K48-linked polyubiquitin chains. A well-recognized function of Peli family members is participation in the signal transduction mediated by Toll-like receptors (TLRs) and IL-1 receptor. Recent gene targeting studies have provided important insights into the in vivo functions of Peli1 in the regulation of TLR signaling and inflammation. These studies have also extended the biological functions of Peli1 to the regulation of T-cell tolerance. Consistent with its immunoregulatory functions, Peli1 responds to different immune stimuli for its gene expression and catalytic activation. In this review, we discuss the recent progress, as well as the historical perspectives in the regulation and biological functions of Peli.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Immune Tolerance
  • Immunomodulation
  • Nuclear Proteins / immunology*
  • Receptors, Interleukin-1 / immunology
  • Signal Transduction* / immunology
  • T-Lymphocytes / immunology*
  • Toll-Like Receptors / immunology*
  • Ubiquitin-Protein Ligases / immunology*


  • Nuclear Proteins
  • Receptors, Interleukin-1
  • Toll-Like Receptors
  • PELI1 protein, human
  • Ubiquitin-Protein Ligases