The ubiquitin ligase Peli1 negatively regulates T cell activation and prevents autoimmunity. Academic Article uri icon


  • T cell activation is subject to tight regulation to avoid inappropriate responses to self antigens. Here we show that genetic deficiency in the ubiquitin ligase Peli1 caused hyperactivation of T cells and rendered T cells refractory to suppression by regulatory T cells and transforming growth factor- (TGF-). As a result, Peli1-deficient mice spontaneously developed autoimmunity characterized by multiorgan inflammation and autoantibody production. Peli1 deficiency resulted in the nuclear accumulation of c-Rel, a member of the NF-B family of transcription factors with pivotal roles in T cell activation. Peli1 negatively regulated c-Rel by mediating its Lys48 (K48) ubiquitination. Our results identify Peli1 as a critical factor in the maintenance of peripheral T cell tolerance and demonstrate a previously unknown mechanism of c-Rel regulation.

published proceedings

  • Nat Immunol

altmetric score

  • 2.5

author list (cited authors)

  • Chang, M., Jin, W., Chang, J., Xiao, Y., Brittain, G. C., Yu, J., ... Sun, S.

citation count

  • 142

complete list of authors

  • Chang, Mikyoung||Jin, Wei||Chang, Jae-Hoon||Xiao, Yichuan||Brittain, George C||Yu, Jiayi||Zhou, Xiaofei||Wang, Yi-Hong||Cheng, Xuhong||Li, Pingwei||Rabinovich, Brian A||Hwu, Patrick||Sun, Shao-Cong

publication date

  • January 2011