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

An Chen, Beixue Gao, Jingping Zhang, Tamara McEwen, Shui Q. Ye, Donna Zhang, Deyu Fang*

*Corresponding author for this work

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5348-5356
Number of pages9
JournalMolecular and cellular biology
Volume29
Issue number19
DOIs
StatePublished - Oct 2009

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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