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The HECT-type E3 ubiquitin ligase AIP2 inhibits activation-induced T-cell death by catalyzing EGR2 ubiquitination.

E3 ubiquitin ligases, which target specific molecules for proteolytic destruction, have emerged as key regulators of immune functions. Several E3 ubiquitin ligases, including c-Cbl, Cbl-b, GRAIL, Itch, and Nedd4, have been shown to negatively regulate T-cell activation. Here, we report that the HECT-type E3 ligase AIP2 positively regulates T-cell activation. Ectopic expression of AIP2 in mouse primary T cells enhances their proliferation and interleukin-2 production by suppressing the apoptosis of T cells. AIP2 interacts with and promotes ubiquitin-mediated degradation of EGR2, a zinc finger transcription factor that has been found to regulate Fas ligand (FasL) expression during activation-induced T-cell death. Suppression of AIP2 expression by small RNA interference upregulates EGR2, inhibits EGR2 ubiquitination and FasL expression, and enhances the apoptosis of T cells. Therefore, AIP2 regulates activation-induced T-cell death by suppressing EGR2-mediated FasL expression via the ubiquitin pathway.

Pubmed ID: 19651900


  • Chen A
  • Gao B
  • Zhang J
  • McEwen T
  • Ye SQ
  • Zhang D
  • Fang D


Molecular and cellular biology

Publication Data

October 11, 2009

Associated Grants


Mesh Terms

  • Animals
  • Apoptosis
  • Biocatalysis
  • Cells, Cultured
  • Early Growth Response Protein 2
  • Ether-A-Go-Go Potassium Channels
  • Fas Ligand Protein
  • Humans
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • RNA, Small Interfering
  • T-Lymphocytes
  • Ubiquitin-Protein Ligases
  • Ubiquitination