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Mol Cell Biol. 2009 Oct;29(19):5348-56. doi: 10.1128/MCB.00407-09. Epub 2009 Aug 3.

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

Author information

1
Departments of Otolaryngology-Head and Neck Surgery and Molecular Microbiology and Immunology, University of Missouri-Columbia School of Medicine, One Hospital Dr., Columbia, MO 65212, USA.

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.

PMID:
19651900
PMCID:
PMC2747983
DOI:
10.1128/MCB.00407-09
[Indexed for MEDLINE]
Free PMC Article

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